oral cancer

John Prine, Who Chronicled the Human Condition in Song, Dies at 73

Source: The New York Times
Date: April 7th, 2020
Author: William Grimes

 

John Prine, the raspy-voiced country-folk singer whose ingenious lyrics to songs by turns poignant, angry and comic made him a favorite of Bob Dylan, Kris Kristofferson and others, died on Tuesday in Nashville. He was 73.

The cause was complications of the coronavirus, his family said.

Mr. Prine underwent cancer surgery in 1998 to remove a tumor in his neck identified as squamous cell cancer, which had damaged his vocal cords. In 2013, he had part of one lung removed to treat lung cancer. He had been hospitalized since late last month.

Mr. Prine was a relative unknown in 1970 when Mr. Kristofferson heard him play one night at a small Chicago club called the Fifth Peg, dragged there by the singer-songwriter Steve Goodman. Mr. Kristofferson was performing in Chicago at the time at the Quiet Knight. At the Fifth Peg, Mr. Prine treated him to a brief after-hours performance of material that, Mr. Kristofferson later wrote, “was unlike anything I’d heard before.”

A few weeks later, when Mr. Prine was in New York, Mr. Kristofferson invited him onstage at the Bitter End in Greenwich Village, where he was appearing with Carly Simon, and introduced him to the audience.

“No way somebody this young can be writing so heavy,” he said. “John Prine is so good, we may have to break his thumbs.”

The record executive Jerry Wexler, who was in the audience, signed Mr. Prine to a contract with Atlantic Records the next day.

Music writers at the time were eager to crown a successor to Mr. Dylan, and Mr. Prine, with his nasal, sandpapery voice and literate way with a song, came ready to order. His debut album, called simply “John Prine” and released in 1971, included songs that became his signatures. Some gained wider fame after being recorded by other artists.

They included “Sam Stone,” about a drug-addicted war veteran (with the unforgettable refrain “There’s a hole in Daddy’s arm where all the money goes”); “Hello in There,” a heart-rending evocation of old age and loneliness; and “Angel From Montgomery,” the hard-luck lament of a middle-aged woman dreaming about a better life, later made famous by Bonnie Raitt.

“He’s a true folk singer in the best folk tradition, cutting right to the heart of things, as pure and simple as rain,” Ms. Raitt told Rolling Stone in 1992.

Mr. Dylan, listing his favorite songwriters in a 2009 interview, put Mr. Prine front and center. “Prine’s stuff is pure Proustian existentialism,” he said. “Midwestern mind trips to the nth degree. And he writes beautiful songs.”

John Prine was born on Oct. 10, 1946, in Maywood, Ill., a working-class suburb of Chicago, to William and Verna (Hamm) Prine. His father, a tool-and-die maker at the American Can Company, and his mother had moved from the coal town of Paradise, Ky., in the 1930s.

Mr. Prine later wrote a ruefully bitter song titled “Paradise,” in which he sang:

The coal company came with the world’s largest shovel
And they tortured the timber and stripped all the land
Well, they dug for their coal till the land was forsaken
Then they wrote it all down as the progress of man

John grew up in a country music-loving family. He learned guitar as a young teenager from his grandfather and brother and began writing songs.

After graduating from high school, he worked for the Post Office for two years before being drafted into the Army, which sent him to West Germany in charge of the motor pool at his base. After being discharged, he resumed his mail route, in and around his hometown, composing songs in his head.

“I always likened the mail route to a library with no books,” he wrote on his website. “I passed the time each day making up these little ditties.”

Reluctantly, he took the stage for the first time at an open-mic night at the Fifth Peg, where his performance of “Hello in There” and “Angel From Montgomery” met with profound silence from the audience. “They just sat there,” Mr. Prine wrote. “They didn’t even applaud, they just looked at me.”

Then the clapping began. “It was like I found out all of a sudden that I could communicate deep feelings and emotions,” he wrote. “And to find that out all at once was amazing.”

Not long after, Roger Ebert, the film critic for The Chicago Sun-Times, wandered into the club while Mr. Prine was performing. He liked what he heard and wrote Mr. Prine’s first review, under the headline “Singing Mailman Who Delivers a Powerful Message in a Few Words.”

“He appears onstage with such modesty he almost seems to be backing into the spotlight,” Mr. Ebert wrote. “He sings rather quietly, and his guitar work is good, but he doesn’t show off. He starts slow. But after a song or two, even the drunks in the room begin to listen to his lyrics. And then he has you.”

Mr. Prine had a particular gift for offbeat humor, reflected in songs like “Jesus, the Missing Years,” “Some Humans Ain’t Human,” “Sabu Visits the Twin Cities Alone” and the antiwar screed “Your Flag Decal Won’t Get You Into Heaven Anymore.”

“I guess what I always found funny was the human condition,” he told the British newspaper The Daily Telegraph in 2013. “There is a certain comedy and pathos to trouble and accidents.”

After recording several albums for Atlantic and Asylum, he started his own label, Oh Boy Records, in 1984. He never had a hit record, but he commanded a loyal audience that ensured steady if modest sales for his albums and a durable concert career.

In 1992, his album “The Missing Years,” with guest appearances by Bruce Springsteen, Tom Petty and other artists, won a Grammy Award for best contemporary folk recording. He received a second Grammy in the same category in 2006 for the album “Fair and Square.”

Mr. Prine, who lived in Nashville, was divorced twice. He is survived by his wife, Fiona Whelan Prine, a native of Ireland whom he married in 1996; three sons, Jody, Jack and Tommy; two brothers, Dave and Billy; and three grandchildren. In 2017, Mr. Prine published “John Prine Beyond Words,” a collection of lyrics, guitar chords, commentary and photographs from his own archive.

In 2019, he was inducted into the Songwriters Hall of Fame, and his album “Tree of Forgiveness” was nominated for a Grammy, for best Americana album. It was his 19th album and his first of original material in more than a decade. (The award went to Brandi Carlile, for “By the Way, I Forgive You.”)

Mr. Prine went on tour in 2018 to promote “Tree of Forgiveness,” and after a two-night stand at the Ryman Auditorium in Nashville — known there as the mother church of country music — Margaret Renkl, a contributing opinion writer for The New York Times, wrote, under the headline “American Oracle”:

“The mother church of country music, where the seats are scratched-up pews and the windows are stained glass, is the place where the new John Prine — older now, scarred by cancer surgeries, his voice deeper and full of gravel — is most clearly still the old John Prine: mischievous, delighting in tomfoolery, but also worried about the world.”

In December, he was chosen to receive a 2020 Grammy for lifetime achievement.

As a songwriter, Mr. Prine was prolific and quick. In the early days, he would sometimes dash off a song while driving to a club.

“Sometimes, the best ones come together at the exact same time, and it takes about as long to write it as it does to sing it,” he told the poet Ted Kooser in an interview at the Library of Congress in 2005. “They come along like a dream or something, and you just got to hurry up and respond to it, because if you mess around, the song is liable to pass you by.”

Featured Image by Chad Batka of the New York Times

April, 2020|Oral Cancer News|

How Marijuana Accelerates Growth of HPV-related Head and Neck Cancer Identified

University of California San Diego School of Medicine researchers have identified the molecular mechanism activated by the presence of tetrahydrocannabinol (THC) — the ingredient that causes people to feel the euphoria or “high” associated with cannabis — in the bloodstream that accelerates cancer growth in patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma.

“HPV-related head and neck cancer is one of the fastest growing cancers in the United States. While at the same time, exposure to marijuana is accelerating. This is a huge public health problem,” said Joseph A. Califano III, MD, senior author and professor and vice chief of the Division of Otolaryngology in the Department of Surgery at UC San Diego School of Medicine.

Head and neck squamous cell carcinoma is the sixth most common cancer worldwide. These cancers begin in the cells that line the mucous membranes inside the mouth, nose and throat. Approximately 30 percent of cases of this disease are related to HPV infection, and it is these cases, in particular that are on the rise. Califano suggested increased marijuana use may be a driving factor.

Previous studies have linked daily marijuana exposure to an increased prevalence of HPV-related throat cancer. However, a mechanism linking cannabis exposure to increased growth of the cancer was unknown.

Reporting in the January 13, 2020 online edition of Clinical Cancer Research, a journal of the American Association for Cancer Research, researchers outline how the presence of THC in the bloodstream activates the p38 MAPK pathway, which controls programed cell death called apoptosis. When activated, p38 MAPK prevents apoptosis from occurring, thus allowing cancer cells to grow uncontrollably.

Working with Chao Liu, MD, visiting scientist at UC San Diego and a physician at China’s Central South University, and other colleagues, Califano and team used animal and human cell lines to show that THC turns p38 MAPK on and were able to stop the growth of HPV-positive head and neck cancer by turning off the pathway.

The team then analyzed blood samples from patients with HPV-related throat cancer who had their genomes comprehensively mapped to define activated gene pathways. Similar to the cell lines, the blood samples showed p38 MAPK activation and loss of apoptosis in tumors from patients with THC in their blood.

The authors said studies and public opinion suggestions that THC and other cannabis products have cancer-fighting properties need additional, more critical evaluation. Past studies showing anticancer effects of THC and other cannabinoids often used levels of THC higher than those found with recreational use, but doses used recreationally clearly activate a cancer-causing pathway, said Califano.

“We now have convincing scientific evidence that daily marijuana use can drive tumor growth in HPV-related head and neck cancer,” said Califano. “Marijuana and other cannabis products are often considered benign, but it is important to note that all drugs that have benefits can also have drawbacks. This is a cautionary tale.”

According to the Centers for Disease Control and Prevention (CDC), HPV infections are responsible for approximately 35,000 new cancer diagnoses each year in the United States. Infection is so common that nearly all men and women will get at least one type of HPV at some point in their lives. Most clear up on their own, without the person ever knowing they’ve had it.

Several vaccines are available that can prevent the majority of HPV-related cancers. The vaccines work best when they are given before a person is exposed to the virus. The CDC recommends vaccinating boys and girls age 11 to 12 years old but it can be administered as early as age 9.

According to the National Institute on Drug Abuse, 15 percent of youth 12 to 17 years old and 47 percent of adults age 26 and older have used or tried marijuana.

Together, a low HPV vaccination rate and an increase in marijuana use among youth has the makings of a storm, said Califano, physician-in-chief and director of the Head and Neck Cancer Center at Moores Cancer Center at UC San Diego Health.

Moores Cancer Center is one of only 51 National Cancer Institute-designated Comprehensive Cancer Centers in the country and the only such center in San Diego County.

Treatment options for patients with early- or late-stage head and neck cancers include minimally invasive surgery, reconstruction and rehabilitation, proton therapy and other radiation therapy, innovative clinical trials and targeted therapy, including immunotherapy.

The Head and Neck Cancer Center provides comprehensive care that includes counseling, education and support groups, nutrition, dental rehabilitation, speech and language therapy and social workers to help patients through every step of the process beginning with diagnosis to support lifelong wellness.

Califano and team are now looking at whether cannabidiol, or CBD, has a similar effect to THC. CBD is another major chemical compound found in marijuana, but does not produce the “high” and is now commonly used in various over-the-counter products, such as lotions, ointments and edibles.

In addition, the team is investigating whether p38 MAPK can be targeted with drugs to stop HPV-related head and neck cancer from growing.

Co-authors include: Chao Liu, Sayed Sadat, Koji Ebisumoto, Akihiro Sakai, Bharat Panuganti, Shuling Ren, Yusuke Goto, Sunny Haft, Takahito Fukusumi, Mizuo Ando, Yuki Saito, Pablo Tamayo, Huwate Yeerna, William Kim, Jacqueline Hubbard, Andrew Sharabi and J. Silvio Gutkind from UC San Diego; and Theresa Guo from Johns Hopkins Medical Institutions.

Funding for this research came, in part, from the National Institute of Dental and Craniofacial Research and National Institute of Health (R01 DE023347, U01CA217885, R01HG009285, R01CA121941 and P30CA023100).

January, 2020|Oral Cancer News|

How the ADA Oral Cancer Policy Amendment Will Affect Your Practice

Source: Dentistry Today
Date: November 29th, 2019
Author: Jo-Anne Jones

The ADA recently announced an expansion to its policy on oral cancer detection recommending that dentists and dental hygienists perform routine examinations for oral cancer includingoropharyngeal cancer for all patients.

Passed by the ADA House of Delegates in September, this change was brought about to align with concerns from the Centers for Disease Control and Prevention (CDC) over the escalating numbers of diagnosed cases of oropharyngeal cancer linked to the human papillomavirus (HPV).

While HPV-related oropharyngeal cancer has risen by 225% over the past two decades, oral cancer linked to the historical etiologic pathways of tobacco and alcohol use has declined by 50%. The ADA’s policy also aligns with support for the HPV vaccine, as 70% of oropharyngeal cancers in the United States are related to HPV, according to the CDC.

Dentists and dental hygienists play a critical role in opportunistic screening on all adult patients despite whether they possess the historical risk factors of using tobacco products or alcohol. There is a distinct knowledge gap in today’s population to fully understand that a non-smoker and non-drinker may in fact be at risk for oral and oropharyngeal cancer due to HPV.

It is our responsibility to educate our dental patients about all of the risk factors that exist for both oral and oropharyngeal cancer. Now more than ever, it is critically important to extend our screening practices, both visual and tactile, to every adult in the practice on an annual basis.

Only about a third of adults in the United States report being screened for oral cancer, representing a strong disconnect in our ability to improve earlier discovery rates and improve treatment outcomes.

As dental professionals, it is critical that we elevate our understanding of the escalating profile of HPV-related oropharyngeal cancer. Researchers once predicted that cases of HPV-related oropharyngeal cancer would surpass the leading HPV-related cervical cancer by 2020. Yet recent data from national registries has now confirmed that HPV-related oropharyngeal cancer became the leading HPV-associated cancer in 2015.

How common is HPV-related oropharyngeal cancer? About 53,000 Americans will be diagnosed with oral and oropharyngeal cancer this year. Close to 20,000 of those cases will occur in the oropharyngeal area, with 70% related to HPV.

The CDC also reports that HPV is so common that almost all sexually active adults will have an infection in their lifetimes, with most of the population clearing the infection with no repercussions. In contrast, a persistent infection with a high-risk strain such as HPV-16 can transform into oral or oropharyngeal cancer.

This transformation may take anywhere between 15 and 30 years. It seems to be targeting a much younger profile of white, non-smoking males age 35 to 55 with a four-to-one incidence of gender predisposition of males over females.

HPV has an affinity for lymphoid tissues and occurs most commonly in the tonsillar areas and the base of the tongue, with a smaller percentage occurring anteriorly in the oral cavity. Due to limited visual acuity, it is important to know and recognize the subtle symptoms that may accompany a posteriorly positioned tumor of HPV origin.

The following symptoms may be among the first distinguishable signs of the presence of oropharyngeal cancer:

  • Bleeding in the mouth or throat
  • Hoarseness or a change in the voice
  • A lump in the throat or the feeling that something is stuck in the throat
  • Continual lymphadenopathy or persistent neck masses despite antibiotic therapy
  • Slurred speech or difficulty articulating certain sounds
  • A tongue that tracks to one side when stuck out
  • Asymmetry in the tonsillar area
  • A persistent or recurring throat infection that doesn’t fully resolve with antibiotics
  • Unilateral earache
  • A persistent cough

Oral cancer can be very subtle, so it is extremely important to use magnification such as loupes and a dedicated light source or headlight to be able to discern early visible changes. The paradox that exists is that abnormal cellular differentiation typically starts at the basement membrane. By the time it becomes visible, it has progressed to a later stage of development.

Tactile palpation is paramount in uncovering any areas of hardness or induration possibly suggesting a mass or a tumor that is not yet clinically visible.

Enhanced oral cancer screening with a device such as the VELscope Vx from Apteryx Imaging may reveal what is not visible to the naked eye. It employs direct fluorescence visualization, which has been used successfully in the cervix, lungs, and colon. Using a proprietary wavelength, it gives clinicians the opportunity to visually penetrate the tissue surface to reveal the basement membrane.

The VELscope Vx is an assessment tool, however, and it does not convey a diagnosis. The golden rule always applies. Any oral abnormality that exists beyond 14 days is suspect and requires referral for further evaluation.

The Oral Cancer Foundation offers comprehensive information to help healthcare professionals and the general public to learn more about HPV’s connection with oral and oropharyngeal cancer. In April of 2019, the group launched the “Check Your Mouth” campaign to educate the public about the importance of self-examination of the oral cavity between dental appointments.

The impetus behind this project was to improve earlier discovery rates by having the public self-refer should they find anything new or abnormal that persists beyond 14 days. Cards may be ordered free of charge from the Oral Cancer Foundation store for distribution to dental patients.

Lastly, sharing information regarding the HPV vaccine is one of the strongest prevention methods we have today to make positive inroads in minimizing this type of cancer. The Food and Drug Administration has approved the HPV vaccine for both boys and girls and expanded the use of Gardasil 9 to include individuals age 27 through 45.

Together, we can have an impact on the earlier discovery of oral and oropharyngeal cancer.

Disclosure: Jo-Anne Jones is a KOL and consultant with Apteryx Imaging.

Ms. Jones is the president of RDH Connection, an educational and clinical training company dedicated to quality education and team training. In the midst of preparing to present her extensive research on HPV-related oropharyngeal cancer to her national association, a loved one was diagnosed with late stage HPV-positive tonsillar cancer and lost her life 16 months later. Jo-Anne proudly partners with the Oral Cancer Foundation in conveying the urgent need for changing the way in which we screen for oral cancer to meet the needs of today’s population. She can be reached at jjones@jo-annejones.com.

Oral HPV DNA Persistence After Head and Neck Cancer Treatment Linked to Disease Progression

Source: genomeweb
Date: May 2, 2019
Author: Staff Reporter

NEW YORK (GenomeWeb) – Persistent traces of human papilloma virus DNA after treatment for HPV-positive head and neck cancer is linked to an increased recurrence risk, a new study has found.

Head and neck cancers affect some 53,000 people in the US each year, according to the National Cancer Institute, and HPV has been implicated in many of those cases. In general, patients with HPV-positive tumors have higher survival rates than those with HPV-negative tumors.

A team of MD Anderson Cancer Center-led researchers collected oral rinse samples from nearly 400 patients with head and neck squamous cell carcinomas at diagnosis and as their treatments progressed. As they reported today in JAMA Oncology, the researchers found that viral load in patients’ oral samples broadly decreased as they underwent therapy. But some patients’ viral loads persisted despite treatment, which was linked to an increased risk of cancer recurrence and death, the researchers reported.

“Our data suggest that a subset of patients with HPV-positive HNSCC at high risk for locoregional recurrence can be identified by detection of persistent, oral HPV after treatment,” MD Anderson’s Maura Gillison and her colleagues write in their paper.

The researchers enrolled 396 patients with oral cavity, oropharyngeal, or unknown primary HNSCC in their study. They tested the patients’ tumors for the presence of 13 high-risk HPV types using an mRNA expression test and found 202 patients had HPV-positive tumors.

At the same time, the researchers collected oral rinse samples from patients at diagnosis, after surgery, and at six months. Additionally, patients who underwent radiotherapy provided weekly oral rinse samples. The researchers tested these samples — a total of 2,922 oral rinse samples — for the presence of HPV using a multiplex PCR-based approach.

At diagnosis, patients with HPV-positive tumors were significantly more likely to have oral rinse samples positive for HPV than were patients with HPV-negative tumors. In particular, the researchers reported that the detection of any oral HPV DNA had a sensitivity of 84 percent, a specificity of 88 percent, a positive predictive value of 88 percent, and a negative predictive value of 84 percent for the diagnosis of an HPV-positive tumor.

The prevalence of oral HPV DNA, though, went down after treatment, the researchers reported. Prior to treatment, the prevalence of HPV DNA in oral rinses that matched that of HPV in the tumor sample was 69 percent. But after primary surgical resection, it was about 14 percent. Its prevalence fell similarly for patients who underwent radiotherapy, going from 85 percent before treatment to 9 percent after radiotherapy.

As expected, overall and recurrence-free survival was higher for patients with HPV-positive tumors than with HPV-negative tumors. Patients with HPV-positive tumors had a two-year overall survival of 91 percent, as compared to 75 percent for patients with HPV-negative tumors.

But for a subset of patients with HPV-positive tumors — about 14 percent — the prevalence of oral HPV DNA didn’t decline with treatment. These patients were more likely to recurrent disease, with about 45 percent experiencing disease recurrence within two years. Additionally, this subset had a lower two-year overall survival of 68 percent.

These patients, the researchers noted, might benefit from increased surveillance or adjuvant therapy.

The researchers added that their findings suggest that oral rinses to detect HPV DNA in head and neck cancer patients might be helpful. They cautioned, though, that its clinical utility might be limited by the need to identify tumor-type infections.

“Ongoing studies will evaluate whether multiplexed detection of plasma HPV DNA can improve these limitations,” the researchers added.

NOTE: This research was paid for in part by the Oral Cancer Foundation,www.oralcancer.org

May, 2019|Oral Cancer News|

CDC: Top HPV-Associated Cancer Is Now Oropharyngeal

Date: 08/23/18
Source: medscape.com
Author: Nick Mulcahy

Oropharyngeal squamous cell carcinoma (SCC) is now the most common HPV-associated cancer in the United States, according to a new report from the Centers for Disease Control and Prevention (CDC) that covers the years 1999 to 2015.

During that period, cervical cancer dropped from being the top HPV-associated cancer and oropharyngeal SCC took its place.

The transition happened because cervical carcinoma incidence rates decreased 1.6% per year, and oropharyngeal SCC incidence rates increased 2.7% per year among men and 0.8% per year among women.

In 2015, there were a total of 11,788 cervical cancers compared with 18,917 oropharyngeal SCCs.

The decline in cervical cancer is a “continued trend since the 1950s as a result of cancer screening,” write the report authors, led by Elizabeth Van Dyne, MD, MPH, an epidemic intelligence service officer at the CDC.

The uptick in oropharyngeal SCC could be due in part to “changing sexual behaviors,” including unprotected oral sex, especially among white men, who report having the highest number of sexual partners and performing oral sex at a younger age compared with other racial/ethnic groups, the authors say.

Oropharyngeal SCCs include those at the base of tongue, pharyngeal tonsils, anterior and posterior tonsillar pillars, glos­sotonsillar sulci, anterior surface of soft palate and uvula, and lateral and posterior pharyngeal walls.

The new report was published August 24 in the Morbidity and Mortality Weekly Report.

The study authors defined HPV-associated cancer as “an invasive malignancy in which HPV DNA was frequently found in special studies.” In other words, the new study data reveal the total number of certain cancers that are associated with — but not necessarily caused by — HPV.

A total of 30,115 new cases of HPV-associated cancers were reported in 1999 and 43,371 in 2015.

Overall, the rate of HPV-associated cancers dropped among women (change, –0.4%) during the study period and rose among men (change, 2.4%).

The CDC analyzed data from their National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program for all years from 1999 to 2015. “These data cover approximately 97.8% of the US population,” say the authors.

However, these two population-based cancer registries have a limitation: They tally invasive cancers but not the HPV status of cancers.

The authors point out HPV causes cervical cancer and “some oropharyngeal, vulvar, vaginal, penile, and anal cancers.”

Table. Annual Change in Type of Cancer From 1999 to 2015

Cancer TypeAverage Annual Change (%)
Cervical–1.6
Vaginal–0.6
Oropharyngeal in men2.7
Oropharyngeal in women0.8
Anal in men2.1
Anal in women2.9
Vulvar1.3

Penile cancer rates remained stable during the study period.

The study authors say that the public health implication of the study is that HPV vaccination “can prevent infection with the HPV types most strongly associated with cancer.”

January, 2019|Oral Cancer News|

Study: Immunotherapy better than chemotherapy for subtype of head and neck cancer

Date: November 30th, 2018
Source: Scienmag

A randomized clinical trial involving 97 medical centers in 20 countries, including Moores Cancer Center at UC San Diego Health, found that treating patients who have chemotherapy-resistant head and neck cancer with the immunotherapy drug pembrolizumab is more effective and less toxic than standard chemotherapy, reports an international team of researchers in the November 30 online issue of The Lancet.

Previous research had shown that pembrolizumab (Keytruda) was safe and effective for treating patients with recurrent or metastatic head and neck squamous cell carcinoma whose disease had progressed while on or after receiving standard chemotherapy. Data from this clinical trial called KEYNOTE-040, a phase III study sponsored by Merck & Co., the manufacturer of the drug, takes the research a step further by comparing the immunotherapy drug head-to-head to three go-to chemotherapy drugs currently used as standard treatment: methotrexate, docetaxel and cetuximab.

“We compared pembrolizumab against standard of care to see if it fulfilled the promise of early data for patients who are unlikely to do well on standard therapy,” said Ezra Cohen, MD, professor of medicine at University of California San Diego School of Medicine and corresponding author on the study.

“In this trial, patients who received pembrolizumab alone had a higher response rate compared to those receiving standard chemotherapy while those responses lasted, on average, one-and-a-half years. Furthermore, the median survival at one year was markedly better. I feel it is safe to say that these types of therapies should be the new standard therapy for people with cancer that recurs and is resistant to therapy.”

Pembrolizumab is an antibody that inhibits the abnormal interaction between the molecule PD-1 on immune cells and the molecule PD-L1 on tumor cells, allowing the immune cells to activate and attack tumors. Similar results were recently published for another anti-PD-1 drug, nivolumab (Opdivo). Both drugs should be considered by treating physicians for patients with this disease, said Cohen.

The study also pointed to potential biomarkers that can guide oncologists to determine which patients are most likely to respond to these anti-PD-1 drugs.

“It’s fairly clear that patients whose tumors express PD-L1 are most likely to benefit from this type of immunotherapy drug,” said Cohen, associate director for translational science at Moores Cancer Center and an internationally recognized physician-scientist who specializes in novel cancer therapies. “In this trial, overall survival was driven by PD-L1 expression. Only patients whose tumors expressed PD-L1 had a response to pembrolizumab and those responses tended to be durable.”

Over a 17-month period, 247 patients were randomized to receive pembrolizumab and 248 patients were randomly selected by their physicians to receive one of the three standard therapies. The median overall survival for patients receiving immunotherapy was 8.4 months and 6.9 months for patients treated with standard care. Patients received treatment until their cancer progressed, they developed unacceptable toxicity, they withdrew or their physician removed them.

The median duration of response was 18.4 months in the pembrolizumab group, compared with five months in the standard therapy group.

Twelve months after initiating the trial, 37 percent of patients receiving pembrolizumab were alive compared to 26.5 percent of patients on standard therapy.

###

Co-authors include: Denis Soulières, Centre Hospitalier de l’Université de Montréal; Christophe Le Tourneau, Institut Curie, INSERM U900 Research Unit, Versailles-Saint-Quentinen-Yvelines University; José Dinis, Instituto Português de Oncologia do Porto Francisco Gentil; Lisa Licitra, Fondazione IRCCS Istituto Nazionale dei Tumori; Myung-Ju Ahn, Samsung Medical Centre; Ainara Soria, Hospital Universitario Ramón y Cajal; Jean-Pascal Machiels, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain; Nicolas Mach, Hôpitaux Universitaires de Genève; Ranee Mehra, Fox Chase Cancer Center; Barbara Burtness, Yale University School of Medicine and Yale Cancer Center; Pingye Zhang, Jonathan Cheng, Ramona F Swaby, Merck & Co; and Kevin J Harrington, The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust, National Institute of Health Research Biomedical Research Centre.

This research was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co. The funder contributed to study design, data collection, data analysis, data interpretation, and the writing of The Lancet paper. The funder maintained the study database. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Disclosure: Cohen reports grant support to the institution from Merck Sharp & Dohme for clinical research related to the submitted work and serving an advisory role for AstraZeneca, Bristol-Myers Squibb, Eisai, Merck, Human Longevity and Pfizer, all outside the submitted work.

December, 2018|Oral Cancer News|

HPV vaccine gains support of ADA

Source: Multi Briefs
Date: October 24th, 2018
Author: Tammy Adams

The American Cancer Society estimates there will be more than 50,000 new cases of oral cancer in 2018. And between 70 to 80 percent of these cases will be attributed to the human papillomavirus virus (HPV), a virus that has types associated with oropharyngeal cancer.

These staggering numbers call for action; action the American Dental Society is willing to take. Why? Because the HPV vaccine could prevent the vast majority of these new cases, but compared to other vaccines in the U.S., it is underutilized.

According to a resolution passed recently by the ADA House of Delegates, the ADA urges dentists to support the use and administration of the human papillomavirus virus vaccine, recognizing it as a way to help prevent infection of the types of HPV associated with oropharyngeal cancer.

Resolution 53H-2018 cites recommendations from the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices. It states that the vaccination is a “safe and effective intervention to decrease the burden of oral and oropharyngeal HPV infection.”

The policy is the result of a multifaceted ADA council proposal that includes input from the Council on Scientific Affairs, the Council on Advocacy for Access and Prevention and the Council on Dental Practice. A workgroup committed to the HPV issue and led by ADA volunteer members developed an evidence-based background report to help write the policy.

Dr. Paul Eleazer, past chair of the ADA Council on Scientific Affairs, said that he is encouraged to see the ADA “get behind” this growing crisis, referring to the rising number of HPV-associated cancers being reported. “There is incontrovertible evidence that this virus is responsible for the sharp uptick in oropharyngeal cancers, especially in younger patients and young adults,” said Dr. Eleazer.

In 2017, the ADA Council on Scientific Affairs and Center for Evidence-Based Dentistry published “Evidence-based Clinical Practice Guideline for the Evaluation of Potentially Malignant Disorders in the Oral Cavity” to inform dental professionals about the potential use of adjuncts as triage tools for the evaluation of lesions, including potentially malignant disorders, in the oral cavity. To view this guideline, visit ADA.org/OralCancer.

To read the full resolution related to the HPV vaccine, members can log in to the Member Center on ADA.org and click on “Committee C—Dental Education, Science and Related Matters” under Reports and Resolutions. It is Resolution 53.

October, 2018|Oral Cancer News|

Long-term implant failure in patients treated for oral cancer by external radiotherapy: a retrospective monocentric study

Source: Journal of Oral Medicine and oral Surgery, JOMOS
Date: October 10th, 2018
Authors: Aline Desoutter, Sophie Deneuve, Sophie-Charlotte Condamin and Anne-Gaëlle Chaux-Bodard

Abstract

Introduction: The placement of dental implants in irradiated bone has allowed functional rehabilitation for many oral cancer patients. Nonetheless, there is only few data about implant failure in irradiated tissues and their consequences. This retrospective study aims to highlight the rate and circumstances of implant failure.

Material and method: Patients treated with external radiotherapy for oral carcinoma and who received dental implants were included. Patients reconstructed with free bone flaps were excluded.

Results: Eighteen patients were included. Forty implants were placed between 2004 and 2007, 8 failed, of whom one osteoradionecrosis was observed. Time interval between radiotherapy and implantation was 44.6 (6–182) months. Mean dose was 51.8 (50–66) Gy.

Discussion: In the series, the implant failure rate is 20%, which corroborates the literature’s data. Failures occur more often for doses over 50 Gy. The placement of dental implant in irradiated bone leads to soft tissue complications but also increases the risk of osteoradionecrosis. The recent reimbursement of dental implants in oral cancer patients by the National Social Health system will probably increase the indications. Multidisciplinary staffs should be aware of benefit/risk ratio for each patient.

Introduction

Dental implants in patients treated for upper aerodigestive tract (UADT) cancers have facilitated the functional and aesthetic rehabilitation of patients whose postoperative anatomy did not allow for the placement of conventional prostheses. Several studies have been conducted and the success rates have varied from 62.5% to over 90% [1]. These success rates would be similar to those found in a healthy patient’s mandible, which is reported to be 92.6% [2]. However, there is little information regarding the types of failures that occur with these implants, as well as the consequences and circumstances surrounding their occurrence, especially when the radiation dose at the implant site is >40 Gy. Indeed, most of the published studies are case studies in which there is great heterogeneity in the initial tumor sites and in the radiation doses received at the implant site. It is therefore difficult to precisely determine the failure risk in patients who have received large radiation doses in the oral area. The expected complications are mainly peri-implantitis, loss of implants, and even osteoradionecrosis (ORN) [3]. The aim of this study was to highlight long-term implant failures in patients who were treated with radiotherapy for oral cancer and to observe the circumstances and consequences of these failures.

Material and methods

The clinical records of oral cancer patients treated between 2004 and 2007 by radiotherapy (exclusively or not) and who received implants were reviewed. In the interest of maintaining the homogeneity of the study sample, patients treated with a microanastomosis fibula flap were excluded.

The following information was extracted from the case records: tumor location, tumor stage, and type of treatment received, the duration between radiotherapy and implantation, the type of implants placed, the surgical and operative protocol, the patient’s medical history (excluding oncology) as well as any implant or peri-implant clinical events and their time of occurrence. Failure was defined as loss of implant osseointegration resulting in implant loss or removal. Surgical and implant loading failures were considered. Statistical analysis was performed using XLSTAT® software (Microsoft).

Results

Eighteen patients, consisting of 14 males (77%) and four females (13%) were eventually included. The mean age at the time of implant placement was 57.5 years (range: 42–78 years).

The initial tumor locations, the initial tumor stage, and the treatments received are presented in Table I.

Table I : Population studied: sites, tumor stages, and treatments received.
Table II : Implant failures as a function of the radiation dose received, initial tumor site, and failure onset delay.

Discussion

Cervicofacial radiation is one of the primary causes of implant loss [1,4] regardless of whether it is administered early or late [5]. Several failure factors specific to implant placement in irradiated areas have been identified; these include the duration after radiotherapy and the radiation dose received.

For successful implantation, the minimum time after radiotherapy before implantation should be 6–12 months [6]. A delay of >12 months would improve implant success rates [7]. In the current study, a minimum period of 6 months was selected after the multidisciplinary consultation with the surgical oncologists and radiotherapists. After excluding the two patients who were treated several years ago, missed their follow-up, and then reappeared for prosthetic rehabilitation, the average implantation time after radiotherapy in our study was 20.37 months (range: 6–49 months). One study [8] showed that the failures are less severe in patients receiving implants a later stage of oncological treatment (17.1% failure rate for intraoperative implants versus 4.6% for those placed postoperatively). Of course, the idea of early rehabilitation encourages the surgical team to perform implantation along with tumor removal, before additional treatments are administered. Although this technique has the advantage of decreasing treatment duration, it is not always feasible because of the constraints of tumor management.

The radiation dose received at the implant site is also a major cause of implant failure, with doses <50 Gy being more favorable [9,10]. Animal studies and literature reviews show that the implant failure rate is directly correlated with the radiation dose received [9,10]. In the study, implant sites that received estimated doses >55 Gy had failure (mean: 59.33 Gy). In fact, all implant failures occurred in patients who received treatment for cancer involving the anterior aspect of the floor of the mouth. The therapeutic target was therefore very close to the implant site, and the dose administered at the implant site was close to the therapeutic dose delivered.

The biggest challenge consists in evaluating the radiation dose received at the implantation site. In most studies, the initial tumor sites involved all the UADTs, including the oropharynx, with low radiation doses of about 30 Gy at the symphyseal and parasymphyseal level. It therefore seems more appropriate to limit the evaluation of failure rates to patients treated for cancer of the oral cavity, as the radiation doses at the implant site are therefore more homogeneous. In published studies, only a few authors [11] highlight the antecedents or lack thereof of radiation, with irradiated tissue implants having osseointegration rates of 83% at 5 years.

Long-term implant survival rates reported by the previous clinical studies are nonhomogeneous, with values of 72.8% at 10 years [9], 24% at 5 years [10], or 72% at 8 years [11]; however, these values support the results of our present study. Thus, Wagner [12] reports a 5-year osseointegration rate of 97.5% and at 10 years of 72.8%, whereas other authors report success rates of 48.3% [3]. Another study reports complications in 41.5% patients [13].

Seven out of eight failures encountered in the series began with peri-implantitis. Werkmeister [14] observed a soft-tissue complication rate of 28.6% in irradiated areas versus 8.3% in nonirradiated areas. These complications can be explained in part by the small amount of keratinized gingiva, along with the predisposing factors of radiotherapy-related sensitization and dry mouth. The occurrence of peri-implantitis should be carefully monitored to avoid ORN [15].

An increased loss of marginal bone was reported by many authors, with 2–9 mm variations for a period of 3 years after implant surgery [16]. According to Tanaka [17], early failures are more frequent. In the studies, all failures occurred >1 year after implant placement.

In the present series, a case of loss of osseointegration resulted in extensive ORN at a rate of 2.5%. Treatment of ORN required a subsequent free vascularized bone transfer reconstruction. This patient had been treated for a mouth floor lesion in the past and had received a postoperative radiation dose of 64 Gy (See Patient 3, Tab. I). This implant failed 1 year previously, and a reimplantation was proposed because of the impossibility of prosthetic rehabilitation without bone anchorage. Thus, there were two interventions on adjacent parasymphyseal mandibular bone sites. The patient had reverted to smoking regularly despite tobacco counseling. The risk of triggering ORN following implant placement was estimated to be 1.6%–5% [9,16,18,19]. Some authors advocate the use of hyperbaric oxygen therapy before and after implantation to stimulate or optimize healing and decrease ORN risk [20,21]. Others believe that the risk/benefit/cost ratio is not sufficiently favorable. More recently, the use of low-intensity pulsed ultrasound to increase healing capacity has been advocated [22]. Animal studies are currently underway [23].

Conclusion

It is widely accepted that the use of implant techniques in cancer patients is sometimes essential to ensure functional prosthetic rehabilitation. This retrospective study, which was conducted on patients who had specifically received oral radiotherapy, confirmed that it was a reliable therapeutic treatment for radiation doses of 45–50 Gy. However, the small number of patients in this study prevents the extrapolation of results to larger populations, considering the significant morbidity and lower success rate than patients who were not irradiated. Thus, the inherent risk of a past history of radiotherapy must be taken into account. The use of software like Dentalmaps® [24] allows a better evaluation of the doses received at potential implantation sites. This software is based on the automatic segmentation and delineation of the dental zones, making it possible to estimate the dose received at different points of the dental arch to the nearest 2-Gy fraction. However, the software is expensive, the work is laborious, and this device cannot be routinely used. Considering that health organizations are responsible for the cost management of implants in patients with cancer of UADT, there will be a definite increase in the indications for implantation [25]. It is up to the members present at the multidisciplinary consultation meetings to evaluate the benefit/risk ratio on a case-by-case basis.

October, 2018|Oral Cancer News|

OCF’s Tobacco Cessation Spokesperson and Bradley Cooper’s Stunt Double Rides in Pendleton

You won’t find Cody Kiser at this year’s NFR, but you will find him working as a stuntman in the 2014 blockerbuster hit “American Sniper” starring Bradley Cooper.

The biographical war drama was directed by Clint Eastwood, and told the story of U.S. Navy Seal Chris Kyle.

Kiser, who rode Saturn Rocket for a 75.5-point score Friday at the Pendleton Round-Up, stepped in for Bradley during the scene that shows Kyle riding broncs during his rodeo days before he joined the Navy.

“That was the coolest thing I have ever done,” Kiser said. “I got to hang out for a day with Clint Eastwood and Bradley Cooper. Clint told me I looked a lot like Bradley. They said they wished they had me for the whole movie.”

A friend of Kiser’s who does stunt work in California put Kiser in touch with the people from the movie.

“They needed a bareback rider who had a certain look,” he said. “They had me and a saddle bronc rider, but he couldn’t ride bareback very well, so the job was mine.”

Kiser, 27, said he was living in Texas near where Kyle was shot in 2013, and that he had a friend working at the Rough Creek Ranch-Lodge in Erath County, Texas, where Kyle was shot.

“It’s such a small world,” he said.

Kiser earned a nice paycheck for his work, but said playing Kyle, even in a stunt role, was an honor.

“To be a part of that was unreal,” he said.

September, 2018|OCF In The News|

Penn-led study raises hopes for vaccine to treat head and neck cancer

Date: 09/21/18
Source: The Inquire, philly.com
Author: Marie McCullough

The patient’s head and neck cancer came roaring back, spreading to his lymph nodes and skin, which developed bleeding tumors. Yet despite a grim prognosis, that man is alive and cancer-free more than two years later.

In a study led by the University of Pennsylvania and published Friday, researchers hypothesize that his remarkable remission is due to a promising combination: an experimental cancer vaccine that activated his disease-fighting T cells, plus Opdivo, one of the revolutionary “checkpoint inhibitor” drugs that cut a brake on the immune system.

“Of course, I’m biased,” said Charu Aggarwal, the Penn oncologist who led the study. “In my career, I haven’t seen a vaccine as impactful as this.”

However, the remission may have been due to Opdivo alone; the study lacks data to rule out that possibility.

Robert Ferris, director of the University of Pittsburgh Medical Center’s Hillman Cancer Center and head of the pivotal study leading to approval of Opdivo, called the Penn-led study “an important intermediate step exploring a strategy that we hope will work.”

Conventional vaccines prevent diseases by priming the immune system to recognize the distinctive “antigens” on invading microbes. Therapeutic cancer vaccines, like the one in this study, are intended to work after cancer develops by provoking a heightened immune response.

Despite decades of research, this approach remains experimental. The only approved product, the prostate cancer vaccine Provenge, was barely effective; the maker filed for bankruptcy in 2015.

A major obstacle to treatment vaccines is the fact that cancer arises from the body’s own cells. Although cancer cells produce antigens as they mutate, using these telltale proteins as targets for the immune system has proved to be very difficult.

Even so, at least four pharmaceutical groups are developing therapeutic vaccines that target human papillomavirus, HPV, the sexually transmitted virus that causes cervical cancer, head and neck cancer, and some rare genital cancers.

These diseases can be warded off with the preventive HPV vaccine that is recommended for all adolescents, but it didn’t exist until 12 years ago. Much to the dismay of public health authorities, vaccination rates remain low. And while screening can detect and treat cervical precancers, there are no early detection methods for head and neck cancers; experts call the surging incidence of these malignancies an “epidemic.”

The vaccine in the new study, called MEDI0457, was originally developed by Inovio with technology pioneered at Penn. In 2015, MedImmune, which is part of AstraZeneca, acquired exclusive rights to the drug.

MEDI0457 contains a DNA ring called a plasmid that programs the patient’s cells to produce two HPV antigens. The vaccine is injected into the patient’s muscle and enters cells with the help of a small electrical pulse applied to the skin. When the cells make the antigens, this triggers the immune system to activate disease-fighting white blood cells, so-called “killer” T cells.

For the study, published Friday in Clinical Cancer Research, 22 patients with head and neck cancer received conventional treatment — either surgery or chemotherapy and radiation — that eliminated all signs of cancer. This was supplemented by four doses of the experimental vaccine, which caused no serious side effects.

Eighteen patients, or 80 percent, showed elevated T cell activity that lasted at least three months after the final vaccine dose. While that is an encouraging sign, the study was too preliminary to detect clinical effectiveness such as tumor shrinkage or improved survival.

In the one patient who relapsed, cancer recurred seven months after vaccine treatment and spread to his lymph nodes and skin. He was given Opdivo and, eight weeks later, the cancer was gone.

Aggarwal and her co-authors note that such remarkable remissions do occasionally occur with checkpoint inhibitors. But they speculate that the vaccine revved up the patient’s T cells, then Opdivo removed the immune brake, enabling the T cells to attack the cancer.

“The response suggests the vaccine may in some manner prime the immune system, potentially boosting the effects of subsequent [checkpoint inhibitor] therapy,” Aggarwal said.

Rajarsi Mandal, director of the head and neck cancer immunotherapy research program at Johns Hopkins University, took a more conservative view: “They demonstrated vaccine specific T cell proliferation very nicely. But there is not a lot of data to suggest the vaccine is inducing any clinical response in these patients. Overall, it’s very interesting, but future studies are needed to demonstrate definitive clinical responses to the vaccine.”

Still, the combination approach is sufficiently promising that MedImmune is now funding a Penn-led clinical trial of MEDI0457 and MedImmune’s own experimental checkpoint inhibitor.

Ferris, meanwhile, said he is part of a trial of a competing experimental vaccine for HPV-related cancers, plus the approved checkpoint inhibitor Keytruda.

“The preventive HPV vaccine works really well,” he said. “But if you’re too old to get it, there is hope that you can stimulate the immune system to fight the cancer. This [new study] suggests the next logical step.”

September, 2018|Oral Cancer News|