Monthly Archives: March 2017

HPV Vaccine Could Protect More People With Fewer Doses, Doctors Insist

Source: www.npr.org
Date: March 29, 2017
Author: Michelle Andrews

You’d think that a vaccine that protects people against more than a half dozen types of cancer would have patients lining up to get it. But the human papillomavirus (HPV) vaccine, which can prevent roughly 90 percent of all cervical cancers as well as other cancers and sexually transmitted infections caused by the virus, has faced an uphill climb since its introduction more than a decade ago.

Now, with a dosing schedule that requires fewer shots of a more effective vaccine, a leading oncology group has joined other clinicians and public health advocates who are pushing hard to prevent these virus-related cancers.

Last year, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommended reducing the number of HPV vaccine shots from three to two for girls and boys between the ages of 9 and 14.

This month, the American Society of Clinical Oncologists also urged physicians in the U.S. and abroad to use the vaccine to help provide protection against cervical cancer.

The CDC recommendation was based, in part, on clinical trial data that showed two doses were just as effective as a three-dose regimen for this age group. (Young people older than 14 still require three shots.)

The clinical trial was conducted using Gardasil 9, a version of the vaccine approved by the Food and Drug Administration in late 2014. It protects against nine types of HPV, seven that are responsible for 90 percent of cervical cancers and two that account for 90 percent of genital warts.

In addition, the improved version of Gardasil increases protection against HPV-related cancers in the vagina, vulva, penis, anus, rectum and oropharynx, which is the tongue and tonsil area at the back of the throat.

An earlier version of the vaccine protected against four types of HPV.

From the start, clinicians have run into some parental and political roadblocks because the vaccine, which is recommended for preteens, protects against genital human papillomavirus, a virus that is transmitted through sexual contact. Many physicians are reluctant about discussing the need for the vaccine, and for many parents, the vaccine’s cancer-prevention benefits have been overshadowed by concerns about discussing sexual matters with young kids.

Yet, for maximum protection, the immunizations should be given before girls and boys become sexually active.

The focus should not have been on sexually transmitted infections, some say. “You only get one chance to make a first impression,” said Dr. H. Cody Meissner, a professor of pediatrics at Tufts University School of Medicine and a member of the American Academy of Pediatrics’ committee on infectious diseases.

“This vaccine should have been introduced as a vaccine that will prevent cancer, not sexually transmitted infections,” Meissner says.

The HPV virus is incredibly common. At any given time, nearly 80 million Americans are infected, and most people can expect to contract HPV at some point in their lives. Most never know they’ve been infected and have no symptoms. Some people develop genital warts, but the infection generally goes away on its own.

However, others may develop problems years later. There are approximately 39,000 HPV-related cancers every year in the U.S., nearly two-thirds of them in women. In addition to cervical cancer, more than 90 percent of anal cancers and 70 percent of vaginal and vulvar cancers are thought to be caused by the HPV virus. Recent studies show that about 70 percent of cancers in the back of the throat, tongue and tonsils may also be linked to HPV.

A 2015 study published in the Journal of the National Cancer Institute estimated that earlier versions of the HPV vaccine could reduce the number of HPV-related cancers by nearly 25,000 annually.

The new vaccine is estimated to prevent 5,000 cancer deaths annually, according to Dr. Paul Offit, professor of pediatrics and director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.

But compliance is an ongoing problem. “They’re not getting the one vaccine that protects against diseases from which they’re most likely to suffer and die,” Offit said, noting that deaths from pertussis and meningococcal disease, for which adolescents are also vaccinated at that age, are minuscule compared with HPV-related cancers.

In 2015, 87 percent of 13-year-olds were up-to-date with the Tdap vaccine that protects against tetanus, diphtheria and pertussis, and 80 percent had received the meningococcal vaccine, according to the CDC. But just 30 percent of girls and 25 percent of boys at that age had received all three doses of the HPV vaccine. In contrast to other vaccines, however, the HPV vaccine is only required in a few states for secondary school students.

Public health advocates say they think the shift to a two-dose regimen could make a big difference for parents, as well as kids.

Because the second HPV shot is supposed to be given anywhere from six months to a year after the first one, “parents can fit it into a routine regimen when people go in for their 12-year-old’s regularly scheduled visit,” said Dr. Joseph Bocchini Jr., chairman of pediatrics at Louisiana State University Health in Shreveport, La. He’s also president-elect of the National Foundation for Infectious Diseases.

 

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

March, 2017|Oral Cancer News|

Immunotherapy Making Its Mark on Head and Neck Cancer

Author: Lisa Miller
Published online: 03/22/2017
Source: http://www.targetedonc.com/

Following the approval of 2 immunotherapy agents, pembrolizumab (Keytruda) and nivolumab (Opdivo) for the treatment of patients with head and neck cancer (HNC) over the last 6 months, immunotherapy is making its mark on the treatment paradigm for HNC.

Due to the responses seen with these 2 agents, immunotherapies are being investigated further in the treatment of HNC.

“Immunotherapy is a very potent treatment for some patients. In a way it shows you that we’re probably just scratching the surface with [immunotherapy treatment for HNC],” Tanguy Seiwert, MD, said during a presentation at the 1st Annual International Congress on Immunotherapies in CancerTM, hosted by the Physicians’ Education Resource (PER).

Findings from the KEYNOTE-012 trial led to the approval of pembrolizumab in patients with recurrent head and neck squamous cell carcinoma (HNSCC). The overall response rate was 18% with only 1 patient experiencing a complete response.1 However, about 50% of patients, both HPV-positive and HPV-negative, experienced a decrease in their target lesions.

“I would like to point out that response is a terrible, terrible outcome measure for immunotherapy. In the end, what we really care about with immunotherapy is overall survival [OS],” commented Seiwert, associate program director of the Head and Neck Cancer Program, and assistant professor of medicine, The University of Chicago Medicine. “Many patients have prolonged stable disease and that likely contributes signicantly to the strong OS signal that we oftentimes see.”

The phase III CheckMate 141 trial, which Seiwert said was “arguably the most important study in the field,” showed a difference in OS that is more revealing of outcome measures in immunotherapy. CheckMate 141 investigated nivolumab monotherapy in the second-line setting versus investigator’s choice of chemotherapy in patients with recurrent or metastatic HNSCC and demonstrated a median OS of 7.5 (95% CI, 5.5-9.1) versus 5.1 months (95% CI, 4.0-6.0) with standard therapy (P = .0101).2 The 1-year OS rate was 36% with nivolumab versus 16.6% with standard therapy. Alternatively, the response rate was 13.3% with nivolumab compared with 5.8% in the standard therapy arm.

“The response rate wasn’t that impressive, but the overall survival data are stunning. And that’s again an example of how wonderfully these drugs work,” Seiwert said.

Following the responses seen in these 2 studies of PD-1 inhibitors, immunotherapy agents are being considered in the frontline, including in combination regimens, which Seiwert believes are promising. One such combination is durvalumab (MEDI4736), a PD-L1 inhibitor, and tremelimumab, an anti–CTLA-4 agent, which was compared against durvalumab or the EXTREME trial regimen of cetuximab (Erbitux) and platinum-based chemotherapy in the phase III KESTREL trial.

Other first-line combination studies of interest in HNC include the KEYNOTE-048 study, which is looking at pembrolizumab and chemotherapy versus pembrolizumab monotherapy or the EXTREME regimen (NCT02358031); the CheckMate 651 study of ipilimumab (Yervoy) and nivolumab versus EXTREME (NCT02741570); and the CheckMate 714 study exploring ipilimumab and nivolumab versus nivolumab as a single agent (NCT02823574).

Preliminary results looking at the combination of lirilumab, an anti-KIR agent, and nivolumab in a phase I/II study were presented at the 2016 SITC Annual Meeting. The combination showed an objective response rate (ORR) of 24.1% versus an ORR of 13.3% seen with nivolumab monotherapy in the CheckMate 141 trial.2,3 The OS at 1 year was 60% with the combination compared with 36% for nivolumab monotherapy. Among patients with PD-L1 expression in the tumor cells of ≥50%, the ORR was 57.1% with lirilumab and nivolumab versus 36.8% with nivolumab alone. Seiwert hypothesized that KIR was among a number of targets, also including CTLA-4, IDO, and OX40, that are more active in hot tumors.

In discussing which patients should receive immunotherapy treatment, Seiwert looked to various biomarkers currently under investigation for their predictive or prognostic association to immu- notherapy response. The KEYNOTE-024 trial looking at pembrolizumab versus chemotherapy in patients with non–small cell lung cancer changed the eld of PD-L1 testing, according to Seiwert. There was a significant difference in progression-free survival (PFS) and OS rates noted in patients with PD-L1 expression of ≥50% on the tumor cells.4 This can be translated into HNC, and notably, the KEYNOTE-048 trial of patients with recurrent or metastatic HNSCC will include a PD-L1–positive subgroup as part of its investigation.

“While I do have my doubts about how perfect PD-L1 testing is, I do believe it plays a role for enrichment,” Seiwert commented.

An interferon-gamma (IFN-γ) signature showed significant association with overall response (P = .005) and PFS (P <.001) in an analysis of PD-L1–positive patients from the KEYNOTE-012 trial.5 There was also a very high negative predictive value for patients with non–IFN-γ–inflamed tumors who did not receive benefit from pembrolizumab, which would prove useful in identifying which patients should not receive anti–PD-1 therapy. Of great interest are the patients with inflamed tumors who do not benefit from the treatment. Perhaps they could be converted into responders through combination therapies, Seiwert pondered.

“None of these biomarkers are perfect. I think we need a bit more time to fully understand this, but these are biomarkers that are potentially helpful and might outperform PD-L1 testing in the near future,” Seiwert said.

 

** OCF was one of the financial sponsors of the checkmate 141 trial that produced BMS’s Opdivo drug (nivolumab).**

March, 2017|Oral Cancer News|

UK cancer patient receives new jaw thanks to 3D printing

Source: http://www.3ders.org/
Author: staff

3D printing techniques are being adopted with increasing regularity in surgery of all kinds, and more and more patients are seeing a hugely improved quality of life thanks to the unique benefits of the technology. The most recent success story took place in the UK, where a patient’s jawbone was entirely reconstructed using bone from his leg. The pioneering surgical procedure made use of 3D printing at various different stages.

Stephen Waterhouse was diagnosed with throat cancer eight years ago, and underwent chemotherapy and radiotherapy in order to fight it. The treatments were a great success and his cancer went away, but they had an unfortunate side effect. His jawbone had started to crumble, and emergency surgery was required before it completely disintegrated. The 53-year-old was taken to Royal Stoke University Hospital, which had purchased a new 3D printer just two years previously.

Costing the hospital trust around £150,000 (about $188K), the machine is the only one of its kind in the country, and was a crucial part of the effort to save the patient’s jawbone. A 3D model was designed from a scan of his remaining intact jaw and printed out as a mold, which was then used to reconstruct the jaw using bone taken from his fibula. The operation lasted around 12 hours and was a great success.

According to Daya Gahir, consultant in maxillofacial and head and neck surgery, the hospital does “at least 40 major head and neck reconstructions per year. Around 10 to 15 cases will be done in this way using the printer.” The procedure is very intricate, and the hospital’s purchase of the 3D printer has revolutionized the way his team operates. “Some of the leg bone was taken then reshaped, as you have to replace bone with bone. We took away some of the skin from the leg as well and replanted it back into the neck. A face is not easy to reconstruct, it is intricate.”

New software for the 3D printer was developed last year, which allows the whole process to be planned and carried out within the hospital. Without this, Stephen may have had to travel to Germany for the operation to be completed, according to Gahir. Using the 3D printer in this way saves a lot of time and effort for patient and medical team alike, as well as cutting costs. Around £11,000 is saved for each case by carrying out the whole surgical process on-site.

Stephen is still in recovery and has praised the care he is receiving from staff, as well as the effectiveness of the surgery. “I am so pleased with the results,” he says, “you can’t tell the difference between the two sides of my mouth.”

March, 2017|Oral Cancer News|

Magnolia man joins exclusive trial in battle against cancer

Source: www.cantonrep.com
Author: Denise Sautters

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

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

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

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

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

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

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

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

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

The tube is temporary until Bartlett heals.

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

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

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

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

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

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

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

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

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

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

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

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

March, 2017|Oral Cancer News|

Self-persuasion iPad app spurs low-income parents to protect teens against cancer-causing HPV

Source: https://medicalxpress.com/news/2017-03-self-persuasion-ipad-app-spurs-low-income.html
Date: March 7, 2017

As health officials struggle to boost the number of teens vaccinated against the deadly human papillomavirus, a new study from Southern Methodist University, Dallas, found that self-persuasion works to bring parents on board.

Currently public health efforts rely on educational messages and doctor recommendations to persuade parents to vaccinate their adolescents. Self-persuasion as a tool for HPV vaccinations has never been researched until now.

The SMU study found that low-income parents will decide to have their teens vaccinated against the sexually transmitted cancer-causing virus if the parents persuade themselves of the protective benefits.

The study’s subjects—almost all moms—were taking their teens and pre-teens to a safety-net pediatric clinic for medical care. It’s the first to look at changing parents’ behavior through self-persuasion using English- and Spanish-language materials.

“This approach is based on the premise that completing the vaccination series is less likely unless parents internalize the beliefs for themselves, as in ‘I see the value, I see the importance, and because I want to help my child,'” said psychology professor Austin S. Baldwin, a principal investigator on the research.

Depending on age, the HPV vaccine requires a series of two or three shots over eight months. External pressure might initially spark parents to action. But vaccinations decline sharply after the first dose.

The new study follows an earlier SMU study that found guilt, social pressure or acting solely upon a doctor’s recommendation was not related to parents’ motivation to vaccinate their kids.

The new finding is reported in the article “Translating self-persuasion into an adolescent HPV vaccine promotion intervention for parents attending safety-net clinics” in the journal Patient Education and Counseling.

Both studies are part of a five-year, $2.5 million grant from the National Cancer Institute. Baldwin, associate professor in the SMU Department of Psychology, is co-principal investigator with Jasmin A. Tiro, associate professor in the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas.

Addressing the HPV problem

A very common virus, HPV infects nearly one in four people in the United States, including teens, according to the Centers for Disease Control. HPV infection can cause cervical, vaginal and vulvar cancers in females; penile cancer in males; and anal cancer, back of the throat cancer and genital warts in both genders, the CDC says.

The CDC recommends a series of two shots of the vaccine for 11- to 14-year-olds to build effectiveness in advance of sexual activity. For 15- to 26-year-olds, they are advised to get three doses over the course of eight months, says the CDC.

Currently, about 60% of adolescent girls and 40% of adolescent boys get the first dose of the HPV vaccine. After that, about 20% of each group fail to follow through with the second dose, Baldwin said.

The goal set by health authorities is to vaccinate 80% of adolescents to achieve the herd immunity effect of indirect protection when a large portion of the population is protected.

NCI grant aimed at developing a software app

The purpose of the National Cancer Institute grant is to develop patient education software for the HPV vaccine that is easily used by low-income parents who may struggle to read and write, and speak only Spanish.

A body of research in the psychology field has shown that the technique of self-persuasion among well-educated people is successful using written English-language materials. Self-persuasion hasn’t previously been tested among underserved populations in safety-net clinics.

The premise is that individuals will be more likely to take action because the choice they are making is important to them and they value it.

In contrast, where motivation is extrinsic, an individual acts out of a sense of others’ expectations or outside pressure.

Research has found that people are much more likely to maintain a behavior over time—such as quitting smoking, exercising or losing weight—when it’s autonomously motivated. Under those circumstances, they value the choice and consider it important.

“A provider making a clear recommendation is clearly important,'” said Deanna C. Denman, a co-author on the study and a graduate researcher in SMU’s Psychology Department. “Autonomy over the decision can be facilitated by the doctor, who can confirm to parents that “The decision is yours, and here are the reasons I recommend it.'”

Doctor’s recommendation matters, but may not be sufficient

For the SMU study, the researchers educated parents in a waiting room by providing a custom-designed software application running on an iPad tablet.

The program guided the parents in English or Spanish to scroll through audio prompts that help them think through why HPV vaccination is important. The parents verbalized in their own words why it would be important to them to get their child vaccinated. Inability to read or write wasn’t a barrier.

Parents in the SMU study were recruited through the Parkland Memorial Hospital’s out-patient pediatric clinics throughout Dallas County. Most of the parents were Hispanic and had a high school education or less. Among 33 parents with unvaccinated adolescents, 27—81%—decided they would vaccinate their child after completing the self-persuasion tasks.

New study builds on prior study results

In the earlier SMU study, researchers surveyed 223 parents from the safety-net clinics. They completed questionnaires relevant to motivation, intentions and barriers to vaccination.

The researchers found that autonomous motivation was strongly correlated with intentions, Denman said. As autonomous motivation increased, the greater parents’ intentions to vaccinate. The lower the autonomous motivation, the lower the parents’ intentions to vaccinate, she explained.

“So they may get the first dose because the doctor says it’s important,” Baldwin said. “But the second and third doses require they come back in a couple months and again in six months. It requires the parent to feel it’s important to their child, and that’s perhaps what’s going to push or motivate them to complete the series. So that’s where, downstream, there’s an important implication.”

More information: Austin S. Baldwin et al. Translating self-persuasion into an adolescent HPV vaccine promotion intervention for parents attending safety-net clinics, Patient Education and Counseling (2016). DOI: 10.1016/j.pec.2016.11.014

March, 2017|Oral Cancer News|