Monthly Archives: February 2016

Immunotherapy Continues to Advance in Head and Neck Cancer

Source: www.onclive.com
Author: Megan Garlapow, PhD
 

Concomitant administration of motolimod with cetuximab (Erbitux) increases the innate and adaptive immune response in the blood and the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC), overcoming negative prognostic biomarkers of cetuximab therapy alone, according to the biomarker data from a recent phase Ib clinical trial that was presented at the 2016 Head and Neck Cancer Symposium. The trial was recently amended to add nivolumab to the combination of cetuximab and motolimod.

Robert-FerrisDr. Robert Ferris, MD PhD

 

“We know that PD-1 and PD-L1 are overexpressed in head and neck cancer, and so it was somewhat irresistible to combine our baseline treatment of cetuximab and motolimod with the PD-L1 inhibition pathway. EGFR itself drives PD-L1, so combining cetuximab with anti-PD-1 inhibitor makes sense. So, we’ve amended this trial. We’re now accruing to treatment with cetuximab, motolimod, and the anti–PD-L1 nivolumab in this trial,” said lead author Robert Ferris, MD, PhD, professor, Departments of Otolaryngology, Radiation Oncology, and Immunology, Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.

According to the authors of the phase Ib data presented at the symposium, the rationale for combining cetuximab with motolimod (VTX2337) as neoadjuvant therapy was that cetuximab induces cellular immunity that correlates with neoadjuvant clinical response. The phase I dose-escalation and safety of the combination had been established (NCT 01334177).

This study of neoadjuvant cetuximab and motolimod had accrued 14 patients with HNSCC that was stage II-IV, resectable, and located in the oropharynx, oral cavity, hypopharynx, or larynx. These patients were biopsied, treated with cetuximab and motolimod for 4 weeks, and then underwent surgery. The endpoints of the trial were the modulation of immune biomarkers.

Interferon-inducible cytokine IP-10 increased after the patients were administered neoadjuvant cetuximab and motolimod (P = .0001). After the neoadjuvant treatment, the peripheral blood lymphocytes had an increased frequency of EGFR-specific CD8 T cells. After the neoadjuvant treatment, regulatory T cells had decreased suppressive receptors and transforming growth factor-β, which induces Foxp3. Also, after the neoadjuvant treatment, circulating MDSCs had decreased PD-L1 (P <.07) and macrophages had increased CD16 expression (P <.07).

After the neoadjuvant treatment with cetuximab and motolimod, genotyping of T-cell receptors showed increased clonality in peripheral blood lymphocytes (P = .003 by Wilcox signed rank test) and tumor-infiltrating lymphocytes (P = .081 by Wilcox signed rank test). Most patients are more oligoclonal than healthy individuals, and some are very clonal with highly prominent expanded clones. Genotyping of T-cell receptors found that clonality was increased by the combination of cetuximab and motolimod compared with treatment with cetuximab alone.

Recent studies have indicated that the PD-1/PD-L1 pathway is upregulated in the HNSCC microenvironment, and that EGFR blockade prevents interferon-γ-mediated upregulation of PD-L1. Thus, this study has been amended to add nivolumab to the adjuvant treatment with cetuximab and motolimod. The endpoints are still the modulation of immune biomarkers.

The aim is to target the tumor microenvironment, such that tumor immune escape is reversed and T cells eliminate HNSCC. Antitumor T cells are reprogrammed to reverse inhibitory signals. Combining the toll-like receptor agonist, motolimod, with cetuximab and with PD-1 pathway inhibitors, such as nivolumab, may enhance the priming and activity of T cells.

“Targeting the tumor microenvironment requires understanding as well as reversal of immune escape mechanisms in the cellular compartment. Reprogramming antitumor T cells to reverse inhibitory signals can be done by directly disrupting those inhibitory signals, the so-called checkpoint receptor field, and can be done potentially by combining proinflammatory signals, such as toll-like receptor agonists, to chemo-attract cells into the microenvironment and to create good inflammation to overcome suppressive factors,” said Ferris.

Recent findings have shown tremendous promise for nivolumab in head and neck cancer. Bristol-Myers Squibb (BMS) announced in January 2016 that nivolumab improved overall survival versus investigator’s choice of therapy for patients with platinum-refractory squamous cell carcinoma of the head and neck in the phase III CheckMate-141 trial. Findings from the study are being discussed with the FDA and other health authorities, according to BMS.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
February, 2016|Oral Cancer News|

Cancer-causing HPV plummeted in teens since vaccine, study finds

Source: www.cnn.com
Author: Sarina Storres
 

(CNN)The human papillomavirus vaccine was first recommended for adolescent girls in the United States in 2006. Since that time, the prevalence of the cancer-causing virus has been dropping among young women, according to a new study.

Researchers at the Centers for Disease Control and Prevention compared the rates of HPV infection in women 14 to 34 years of age during the years before the vaccine was recommended, between 2003 and 2006, with the most recent years for which data are available, 2009 to 2012.

Among girls 14 to 19 years old, rates of infection with the four types of HPV included in the 4vHPV vaccine decreased from 11.5% to 4.3%. There was also a drop, although smaller, in women 20 to 24 years old, from 18.5% to 12.1%. Among the older groups, women ages 25 to 29 and 30 to 34, the prevalence of these HPV types did not change and was about 12% and 9%, respectively.

“These results are very encouraging and show the effectiveness of the vaccine,” said Dr. Lauri E. Markowitz, a medical epidemiologist at the CDC and lead author of the study, which was published Monday in the journal Pediatrics. “Eventually we expect to see decreases in HPV in older groups as women who were young (enough to get the vaccine) age,” Markowitz added.

Among the 14- to 24-year-old women in the study who were sexually active, rates of infection with the HPV types in the vaccine was only 2.1% among those who were vaccinated, compared with 16.9% among their unvaccinated counterparts.

The CDC Advisory Committee on Immunization Practices recommends the three-dose HPV vaccine for girls, and as of 2011 also boys, 11 to 12 years of age. The vaccine is recommended for women and men up to ages 26 and 21, respectively.

The researchers found that 51% of girls 14 to 19 years old reported having received at least one dose of the HPV vaccine. Rates were 33% and 15% among the women 20 to 24 and 25 to 29, respectively. Among the 30- to 34-year-olds, only 3% said they had gotten the vaccine because they were generally too old to receive it by the time it was first recommended.

There are signs that rates of HPV vaccination are on the rise. National surveys reported that the number of girls 13 to 17 years of age who received at least one dose of the HPV vaccine climbed from 44% in 2009 to 54% in 2012.

More vaccine coverage coming

In keeping with the trend toward greater vaccine coverage, an earlier study by Markowitz and her colleagues found that the prevalence of HPV types was 5.1% among 13- to 17-year-olds between 2007 and 2010, the first years after the vaccine was available, slightly higher than the 4.3% in the current study among 14- to 19-year-olds between 2009 and 2012. The waning prevalence of HPV among adolescent girls in more recent years is probably the result of more adolescent girls getting the HPV vaccine, Markowitz said.

However, among women in their 20s and 30s, there was no decrease in the prevalence of HPV between 2007 and 2010, compared with 2003 to 2006, because these women were already too old to receive the vaccine when it became available.

It may be possible for HPV to go the way of other largely eliminated infectious diseases in the United States such as measles, but only if vaccination rates improve, Markowitz said. The CDC is working with many groups, including large medical organizations such as the American Cancer Society, to increase knowledge among health care professionals and give them guidance for talking with families about the vaccine.

“Like all vaccines, having a strong recommendation by the clinician is one of greatest predictors of getting vaccinated,” Markowitz said.

It’s important for patients and parents to think of the HPV vaccine as another one of the vaccines that you get, like those for measles, mumps and rubella, said Dr. Sarah Feldman, co-director of ambulatory gynecologic oncology at Brigham and Women’s Hospital.

There have been some safety concerns, though unfounded, about the HPV vaccine, but the bigger issue is probably that parents shy away from vaccines for young children that protect against sexually transmitted diseases, Feldman said. But as people become more familiar with the vaccine, Feldman hopes there will be less focus on how HPV is transmitted. “We don’t talk about sexual activity as a way of transmitting hepatitis B, we just give the vaccine,” so when children get older and become sexually active, they are protected, she said.

“More and more, it’s becoming clear that this is a cancer prevention vaccine, and if we could get 100% of our boys and 100% of our girls vaccinated, we could probably eradicate the worst HPV types,” Feldman said.

New HPV vaccine

The current study did not detect a difference in rates of infection with HPV types other than the types present in the 4vHPV vaccine, or another vaccine called 2vHPV. Both vaccines include the two HPV types responsible for 66% of cervical cancers in the United States. Markowitz suspects that it is still possible that some cross-protection is happening, if, for example, other HPV types look similar enough to the types in the vaccine that the immune system recognizes them.

However, this question is largely a moot point now that many people in the United States are receiving a new HPV vaccine called 9vHPV, approved in 2014, which protects against a total of nine HPV types, said Dr. Rebecca B. Perkins, associate professor of obstetrics and gynecology at Boston University School of Medicine and Boston Medical Center.

The Advisory Committee on Immunization Practices included 9vHPV as an option in this year’s immunization schedule, along with 4vHPV and 2vHPV. The 9vHPV vaccine protects against five additional cancer-causing HPV types, giving it the potential to prevent about 90% of HPV-associated cancers.

But even with the earlier forms of HPV vaccines, “the vaccine is doing exactly what it’s supposed to,” Perkins said. The current study is a “really strong call to get people vaccinated,” she added.

HPV vaccination could benefit more groups than in the current study, and in more ways. The CDC researchers are planning to look at the rates of HPV infection in males after the vaccine was recommended for boys in 2011. “You should expect to see similar effects in men because trials showed the vaccine worked as well in men as women,” Perkins said.

The CDC researchers are also going to look at rates of oral HPV infection since the HPV vaccine became available. A clinical trial suggested that the vaccine could effectively prevent throat cancers associated with HPV. These cancers are becoming increasingly common, and the trial predicted that in the next few decades, there will be more cases of oral cancers caused by HPV in the United States than cervical cancer.

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

February, 2016|Oral Cancer News|

NCCN Is ‘Vague,’ So Study Clarifies H&N Cancer Follow-up

Source: www.medscape.com
Author: Nick Mulcahy
 

Clinical guidelines can sometimes be slow to respond to epidemiology.

Take the case of oropharyngeal cancers that are associated with human papillomavirus (HPV) infection. They are increasingly common in the United States and, as several studies have demonstrated, have better survival than cancers of this type that are not HPV-positive.

Nonetheless, one of the beacons in oncology care, the National Comprehensive Cancer Network (NCCN), recommends the same follow-up care guidance for oropharynx squamous cell carcinoma whether it is associated with HPV or not, according to two experts.

For post-treatment follow-up, including recurrence detection, “the NCCN guidelines are one-size-fits-all,” said Jessica Frakes, MD, a radiation oncologist at the Moffitt Cancer Center and Research Institute in Tampa, Florida.

She spoke during a press briefing at the Multidisciplinary Head and Neck Cancer Symposium 2016 in Scottsdale, Arizona.

“You are exactly right: the NCCN is fairly vague about when to perform imaging,” said Christine Gourin, MD, an otolaryngologist at Johns Hopkins University in Baltimore, who moderated the press briefing.

Dr Frakes and her colleagues have stepped into this informational breach with a new study that might help clinicians gain clarity on the use of surveillance imaging in HPV-positive oropharyngeal cancer and reduce its frequency.

“The purpose of our study is to determine when these patients fail and when they have side effects so we know how to guide optimal follow-up,” Dr Frakes explained.

The study authors examined 246 cases of nonmetastatic HPV-positive oropharynx squamous cell carcinoma treated with radiation therapy at Moffitt from 2006 to 2014. Most patients (84.6%) received radiation therapy and a concurrent systemic therapy; a minority (15.4%) received radiation alone. Most patients had locally advanced disease.

The team’s major finding was that the great majority of recurrences and toxicities can be detected with imaging 3 months after treatment with definitive radiation therapy and physical exams during the 6 months after treatment.

Specifically, all six local failures were detected by sight or with flexible laryngoscopy conducted during physical exams in that 6-month period.

Eight of the nine regional recurrences (89%), 12 of the 13 locoregional failures (92%), and 15 of the 21 distant recurrences (71%) were detected from symptoms or with a PET/CT scan 3 months after treatment

“For most patients with HPV-associated oropharynx cancer, after a negative 3-month PET scan, physical exams with history and direct visualization are sufficient to find recurrences,” said Dr Frakes in a press statement.

The findings — and the suggestion that PET scans can be suspended after 3 months — are akin to what happens in clinical practice at Johns Hopkins, Dr Gourin reported.

“We have stopped routinely imaging patients after 3 months if a PET is negative, and it’s true that we do pick up more recurrences clinically than radiologically,” she said.

Cutting down on PET scans in this patient population is a good thing, suggested Dr Gourin. “I think we probably do too much post-treatment surveillance imaging,” she said.

There are multiple benefits to suspending imaging, including potentially lowering patient stress because they know their recurrence risk is low and don’t have anxiety related to test results.

Plus, there is a cost reduction.

“A PET scan costs $1500 [for the patient],” said Dr Frakes. Dr Gourin noted that the test is even more expensive in her geographic region.

Factors That Increase Recurrence Risk

The study authors also identified disease characteristics that increase the likelihood of recurrence.

Both regional and distant failures were more common in patients who presented with five or more positive lymph nodes or who had level IV lymph nodes (P < .05).

And the risk of developing distant metastases was greater in patients with a lymph node larger than 6 cm or with bilateral lymphadenopathy (P < .05).

But overall, the results are “excellent,” said Dr Frakes. Within 3 years, the rate of local control was 97.8%, of regional control was 95.3%, of locoregional control was 94.0%, and of freedom from distant metastases was 91.4%. The rate of 3-year overall survival was 91.0%.

Toxicities were also low, which is an endorsement of the multidisciplinary care, said Dr Frakes.

Only 9% of patients experienced severe late toxicities, including 19 grade 3 toxicities and two grade 4 toxicities. These were resolved in 16 of 21 toxicities (76%) at the time of last follow-up.

Most of the toxicities and/or recurrences (64%) occurred in the first 6 months after treatment; only four events occurred more than 2 years after treatment.

Dr Gourin questioned the low rate of serious late toxicities seen with this nonsurgical management of patients. Such a low rate “has not been our experience” at Johns Hopkins, she said.

Dr Frakes and Dr Gourin have disclosed no relevant financial relationships.

Multidisciplinary Head and Neck Cancer Symposium (MHNCS) 2016: Abstract 6. Presented February 19, 2016.

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

February, 2016|Oral Cancer News|

Study: HPV vaccine reduces HPV incidence in teenage girls

Source: www.upi.com
Author: Stephen Feller
 
Study-HPV-vaccine-reduces-HPV-incidence-in-teenage-girlsJust over half of girls have received the HPV vaccination, but a new CDC study shows it has significantly reduced prevalence of the cancer-causing STI among females who have received the vaccine when compared with those who have not. Photo by Adam Gregor/Shutterstock

 

WASHINGTON, Feb. 22 (UPI) — The prevalence of human papillomavirus infection among teenage and young adult women is down nearly two-thirds since the U.S. Centers for Disease Control and Prevention started recommending vaccine in 2006, according to a new study.

The study is the first to show a drop in prevalence among women in their 20s, and continues to show decreases seen in smaller studies during the last few years, but researchers say the effect could be much stronger.

The vaccine is recommended by the CDC and other organizations for girls and boys starting at age 11, experts say, in order to protect children from HPV before they become sexually active and can become infected.

Concerns that the vaccine would influence teens’ sexual practices have also been unfounded, as research has shown the vaccine does not make children more likely to engage in risky sexual behavior, based on a the lack of an increase in other STI incidence among vaccinated girls.

“It’s just like putting on your seatbelt before turning on the car,” Dr. Alix Casler, medical director of pediatrics for Orlando Health, told UPI. She suggests separating the adolescents’ eventual discovery of sex from the effort to prevent life-threatening diseases.

Recommendations for the HPV vaccine — Cervarix, Gardasil and Gardasil 9 — have been expanded to boys, because of the wide range of cancers for which HPV increases risk, including cervical, anal, head and neck cancer, though a 2015 study showed vaccination rates remain relatively low, with just 57 percent of eligible girls and 35 percent of boys vaccinated.

“We are continuing to see decreases in the HPV types that are targeted by the vaccine,” Dr. Lauri Markowitz, a medical epidemiologist at the CDC, told CBS News. “We have seen declines in genital warts [caused by HPV] already. The next thing we expect to see is a decline in pre-cancers, then later on declines in cancer.”

For the study, published in the journal Pediatrics, used survey information collected as part of the National Health and Nutrition Examination Survey between 2003 and 2006 and between 2009 and 2012 on females between the ages of 14 and 34.

The researchers compared prevalence of HPV between the pre-vaccine group before 2006 and post-vaccine group after the vaccine was introduced, finding HPV prevalence declined by 64 percent, from 11.5 percent to 4.3 percent, in girls between age 14 and 19, and by 34 percent, from 18.5 percent to 12.1 percent, among women age 20 to 24.

Among women aged 14 to 24, the prevalence of HPV among vaccinated women, at 2.1 percent, was also significantly lower than the 16.9 percent of unvaccinated women with the STI.

The research is based on the 4vHPV vaccine, which protects against the four most common forms, though the 9vHPV vaccine was approved by the FDA for use to prevent more forms of HPV.

Casler said data in the next several years is likely to show continuing decreases in HPV prevalence as more adolescents receive the vaccine, however some pediatricians are hesitant because of personal bias. Many parents also are nervous the vaccine will act as a message to teens that sex is OK, making some parents want to delay vaccination until their adolescents are sexually active — by which time it may be too late.

“The infection is sexually transmitted, but that doesn’t need to be part of the conversation,” Dr. Joseph A. Bocchini, a pediatric infectious disease specialist at Louisiana State University, told the New York Times. “If a parent is concerned, physicians should be prepared to talk about it. But we don’t really discuss how people become infected with every vaccine-preventable disease.”

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

February, 2016|Oral Cancer News|

ASTRO: Study maps distinct molecular signatures of HPV-positive throat cancer patients by smoking status

Source: www.dotmed.com
Author: ASTRO
 

Scottsdale, Ariz., February 18, 2016, ASTRO — Throat cancer patients exposed to both human papillomavirus (HPV) and tobacco smoke demonstrate a pattern of mutations along several key cancer genes, according to research presented today at the 2016 Multidisciplinary Head and Neck Cancer Symposium. These distinct molecular profiles of heavy and light smokers who develop HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) may inform decisions related to treatment intensity by establishing additional prognostic criteria for this subset of patients.

Researchers examined the molecular characteristics of OPSCC caused by HPV in an effort to determine which DNA mutations predict lower disease free and survival rates among HPV-positive throat cancer patients who smoke. Whereas most patients with OPSCC caused by HPV have an excellent prognosis for disease free survival, those who also smoke generally face more dire prognoses.

The 66 cases of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) in this study were split into heavy and light smoking behavior groups based on pack years. This metric of smoking frequency over long stretches of time is determined by multiplying the number of years a person has smoked by their average number of packs of cigarettes smoked per day. Forty of the 66 patients reported more than 10 pack years (e.g., more than one pack per day for 10 years or two packs per day for five years), and 26 patients reported fewer than 10 pack years.

“Throat cancer patients who smoked and had a history of fewer than 10 pack years had significantly better disease free and overall survival rates than the heavier smoking group,” said Jose P. Zevallos, MD, MPH, FACS, assistant professor and director of oncologic research in the division of head and neck surgical oncology at the University of North Carolina, Chapel Hill and member of the Lineberger Comprehensive Cancer Center. “Our analyses identified several key differences in molecular mutational profiles of the two groups that may shape these outcomes.”

Overall mutation rates were higher for HPV-positive OPSCC patients in the >10 pack year group than those in the <10 pack year group. HLA-A mutations occurred more often in the heavy smoking group, and mutations associated with tobacco exposure and poor survival occurred almost exclusively within the heavy smoker group, including those in TP53 (6 percent vs. 0 percent, p = 0.428), CDKN2A (2 percent vs. 0 percent, p = 0.758), FAT1 (14 percent vs. 6 percent, p = 0.688), CASP8 (8 percent vs. 0 percent, p = 0.565), NOTCH1 (18 percent vs. 0 percent, p = 0.092), FGFR3 (10 percent vs. 0 percent, p = 0.325), and KRAS (4 percent vs. 0 percent, p = 0.232) genes. Researchers on the study note that these are preliminary data and that they are currently recruiting additional participants to add to the small sample size and fully power the between-group tests.

“I think what is most striking is that these genes are mutated almost exclusively in smokers,” said Dr. Zevallos. “This molecular profile suggests that while HPV-positive OPSCC carcinogenesis initiates similarly, tumors in patients who smoke acquire novel mutations not traditionally associated with HPV-associated cancers.” Analyses indicated that the molecular profile of HPV-positive smokers bears similarities to the profile for HPV-negative head and neck cancer, although the profile does maintain several important molecular characteristics of HPV-positive cancer, including frequent PIK3CA and MLL-3 mutations.

Differences in immune-related and tobacco-related gene mutations by smoking status identified in this study may explain why HPV-positive cancer in smokers may be more aggressive. Findings could impact which treatment options are recommended to HPV-positive OPSCC patients by informing clinical trials to establish new molecular parameters to guide determinations of treatment intensity.

“Because HPV-positive throat cancers respond well to treatment, patients often are given the option of choosing less aggressive treatment with fewer side effects,” explained Dr. Zevallos. “Our study begins to set criteria-based changes in tumor DNA that can be used to predict more aggressive cases that should be given more intense treatment. We hope that this information will one day help to guide more personalized treatments for HPV-positive throat cancers.”

Cases were drawn from a North Carolina population-based epidemiologic study conducted from 2001 to 2006 and were examined for mutations across more than 800 genes. Mutations were measured against the Catalogue of Somatic Mutations in Cancer (COSMIC), an online database of information on mutations in an expert-curated selection of key cancer genes that is maintained by the Sanger Institute as part of its Cancer Genome Project. Somatic mutations, which do not occur in reproductive cells and therefore are not passed on to children, were compared for both frequency and copy number variations, as well as their association with survival outcomes.

The abstract, “Molecular Profile of HPV-positive Oropharyngeal Squamous Cell Carcinoma Stratified by Smoking Status,” will be presented in detail during the K. Kian Ang Commemorative Plenary Session on Thursday, February 18, 2016, at 10:30 a.m. Mountain time at the 2016 Multidisciplinary Head and Neck Cancer Symposium in Scottsdale, Arizona. To speak with Dr. Zevallos, contact the ASTRO media relations team at 480-905-7935 (February 18-19 only), 703-286-1600 or press@astro.org.

 
The 2016 Multidisciplinary Head and Neck Cancer Symposium is sponsored by the American Society for Radiation Oncology (ASTRO), the American Society of Clinical Oncology (ASCO) and the American Head & Neck Society (AHNS). The two-and-a-half day meeting includes interactive educational sessions focused on topics such as novel multidisciplinary therapies, directed therapy, treatment guidelines, prevention, surveillance and supportive care, as well as 13 oral abstract presentations of the current science of relevance to the head and neck cancer community. A total of 262 abstracts will be presented, including 249 posters. Keynote speakers include Tanguy Seiwert, MD, of the University of Chicago, to present “Immunotherapy for Head and Neck Cancer;” Robert I. Haddad, MD, of Brigham and Women’s Hospital, to present “Personalized Treatment for Head and Neck Cancer — The Time is Now;” Quynh-Thu Le, MD, FASTRO, of the Stanford School of Medicine, to present “Precision Therapy in Head and Neck Cancer — From Technology to Biomarker-based Risk Stratification;” and Neil Hayes, MD, MPH, of the UNC School of Medicine, to present “Genome Atlas and Sequencing Data: How We Use This Going Forward.”

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

 

February, 2016|Oral Cancer News|

Excitement at new cancer treatment

Source: www.news.doximity.com
Author: James Gallagher
_88291939_c0151810-acute_lymphoblastic_leukaemia,_micrograph-splA therapy that retrains the body’s immune system to fight cancer has provoked excitement after more than 90% of terminally ill patients reportedly went into remission.

 

White blood cells were taken from patients with leukaemia, modified in the lab and then put back.

But the data has not been published or reviewed and two patients are said to have died from an extreme immune response.

Experts said the trial was exciting, but still only “a baby step.”

The news bubbled out of the American Association for the Advancement of Science’s annual meeting in Washington DC.

The lead scientist, Prof Stanley Riddell from the Fred Hutchinson Cancer Research Centre in Seattle, said all other treatments had failed in these patients and they had only two-to-five months to live.

He told the conference that: “The early data is unprecedented.”

Re-training

In the trial, cells from the immune system called killer t-cells were taken out of dozens of patients. The cells normally act like bombs destroying infected tissue.

The researchers genetically modified the t-cells to engineer a new targeting mechanism – with the technical name of chimeric antigen receptors – to target acute lymphoblastic leukaemia.

Prof Riddell told the BBC: “Essentially what this process does is, it genetically reprograms the T-cell to seek out and recognise and destroy the patient’s tumour cells.

“[The patients] were really at the end of the line in terms of treatment options and yet a single dose of this therapy put more than ninety percent of these patients in complete remission where we can’t detect any of these leukaemia cells.”

But one cancer expert told me they still felt in the dark on the full significance of the study, as the data is not available.

Also seven of the patients developed cytokine release syndrome so severe that they required intensive care, and a further two patients died.

While those odds may be acceptable if facing terminal cancer, the side-effects are much greater than conventional leukaemia treatments such as chemotherapy and radiotherapy, which work in the majority of patients.


Analysis

By James Gallagher, health editor, BBC News website

The field of immunotherapy – harnessing the immune system to attack cancer – is coming of age.

The significance of today’s development is hard to ascertain while the data is unpublished – but the field is undoubtedly making giant strides.

Drugs called checkpoint inhibitors, such as pembrolizumab and ipilimumab, take the brakes off the immune system so it attacks cancer.

They are already being used by doctors.

And other experimental techniques are coming to fruition to allow doctors to change a patient’s own cells to engineer a designer immune system to kill cancer.

It’s an exciting time that is likely to see immunotherapy soon join chemotherapy, radiotherapy and surgery as major weapons in the fight against cancer.


There is also a big difference between using such approaches on a blood cancer like leukaemia and “solid” tumours such as breast cancer.

Dr Alan Worsley, from Cancer Research UK, said that while the field was incredibly exciting, “this is a baby step”.

He told the BBC: “We’ve been working for a while using this type of technology, genetically engineering cells. So far it’s really shown some promise in this type of blood cancer.

“We should say that in most cases standard treatment for blood cancer is quite effective, so this is for those rare patients where that hasn’t worked.

“The real challenge now is how do we get this to work for other cancers, how do we get it to work for what’s known as solid cancers, cancers in the tissue?”

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

**Note: While OCF has included this general media news report in our oral cancer news feed, we wish our readers to note the many caveats in it. A few patents had extreme reactions to the immuno therapy, including death. And the data has not been published, so outside of the group that conducted this research, there have been no professional commentaries on the trial, which perhaps might offer counterpoints. Also, for us in the oral and oropharyngeal  world of solid tumors we have no idea if this could work. Certainly these patients with only months to live, thought like I would. Why not try, I might win the lottery (as some certainly did) and if it doesn’t work, I have in my demise provided scientific insight that might help others behind me on this path.  But even in that group we do not yet know if these remissions will be robust and durable over a long period of time, or if there are to be in the coming years some new catastrophic issue related to the treatment. This is indeed an exciting time in cancer research. But as OCF continues to put stories and actual clinical data about these approaches up in our news stream, please remember that we are in the infancy of our knowledge and understanding of all this. These are not currently first line treatment ideas, many will be in the realm of clinical trial settings for years, and not available to most. While I am very fortunate to sit on the National Cancer Institute Oversight Committee on Immunotherapeutics  in Head and Neck Cancers, I was reminded the other day by a colleague trying to keep my expectations in perspective. He said – remember the charts that were available to Columbus when he set sail for the new world.  Out in the middle of the ocean there was a notation that said “Beyond here there be sea monsters…… as many ships had set to sea and many were never heard from again. And we are finding ourselves in slightly similar circumstances. Chimera antigens, and much more are giving us a glimpse of what MAY be just over the horizon.  Fortunately, I said….he landed safely on a new land, and the world that was known was changed forever.  These are indeed exciting times of great promise, but there is hard work to do still on the table.  OCF and its donor supported researchers are on the cutting edge of the current thoughts, and all of us together will hopefully find ourselves standing on that distant shore, and the world we know today will be forever changed.  Brian Hill

February, 2016|Oral Cancer News|

A small revolution in cancer treatment by Belarusian and U.S. scientists

Source: http://eng.belta.by/
Author: Igor Belotserkovsky

Scientists from Belarus and the United States have developed a new method for detecting residual cancer cells. This method also contributes to their destruction. This is done with the help of nanobubbles generated in some cancer cells. The method was successfully tested on laboratory mice with implanted head and neck cancer cells. Although scientists are only at the beginning of the road, they call their discovery a small revolution in the fight against cancer.

The results of the research titled “Intraoperative diagnostics and elimination of residual microtumors with plasmonic nanobubbles” was published in the prestigious science journal Nature Nanotechnology on 15 February. To learn more about the successes of oncologists, BelTA talked to Igor Belotserkovsky, PhD in Medical Sciences, one of the authors of the research, the leader of the head and neck tumor research team at the Aleksandrov National Cancer Center.

Mr Belotserkovsky, what is the share of head and neck tumors in the structure of other localizations?
In the total structure of oncological morbidity, the share of head and neck tumors is 3-4% (excluding skin cancer). Larynx and oral cavity cancer are diagnosed most frequently. For example, in 2014 laryngeal cancer was detected in 604 Belarusians, oro-pharyngo-laryngeal cancer in 1,338 people. Men fall ill ten times more often.

Despite the fact that head and neck cancers are categorized as tumors of outside localization, many patients with cancer have their disease diagnosed when it has already reached an advanced stage. This is due to the social aspect. In most cases cancer patients are alcohol and smoking abusers. In 2014, 50% of laryngeal cancer cases were found at an early stage, as was 30% of cases of oral cavity cancer.

Why has it been decided to test the new method specifically on head and neck tumors?
Head and neck account for 9% of the total body surface area. Yet, this is where many important organs are located. If one of these organs is affected by cancer, oncologists have to work in a small body region. When removing a tumor, a surgeon cannot cut out much of the normal tissue surrounding it. He has to remove the parts affected by cancer and ensure no damage is done to vitally important structures.

For this reason, the radicality of head and neck cancer surgeries is strongly debated. Some reputable specialists believe that many head and neck surgeries are conditionally radical. We remove the visible tumor, and some unnoticed microscopic metastatic cancer cells may remain in the body. These cells cause cancer recurrences that are more difficult to treat, because they are more resistant to drugs, chemotherapy, and radiation therapy.

What is special about this new treatment method?
Its breakthrough nature is seen in our ability to spot and eliminate residual cancer cells during the surgery, right after the removal of the visible tumor. Today there is no fast, accurate and safe method for detection of individual cancer cells and microtumors in the tumor removal zone to be used during the surgery.

The method is based on the utilization of gold nanoparticles and laser radiation to generate nanobubbles inside tumor cells. The nanobubbles, in turn, are detected with an acoustic probe. For this purpose, the gold nanoparticles are decorated with special antibodies that identify cancer cells and gather in clusters only around the tumor, thereby ensuring no damage is done to healthy tissue.

The approach has been successfully tested on lab mice. The animals of the research and control groups underwent the same operations to remove implanted head and neck tumors. With additional minimal surgery conducted after detection of residual cancer cells with plasmonic nanobubbles, the survival rate in the research group was 100%. Meanwhile, the control group mice underwent only a standard surgery and died of progressing tumor. By the way, nanobubbles helped eliminate inoperable microtumors.

The idea is to reduce the frequency of tumor recurrence. The procedure is as follows: a patient gets an injection with gold nanoparticles before the surgery. After the tumor is removed, the tumor bed is treated with laser which activates nanobubbles that quickly expand and burst, ripping apart the residual cancer cells.

We expect that the new method will help reduce the number of local recurrences. It will allow a maximum radical removal of tumors. Oncologists will be able to eliminate cancer cells, which may cause recurrences, at the microlevel.

When do you plan clinical tests?
We are ready to conduct the tests, here in Belarus. Our center has a high level of credibility in research. Foreign companies annually run nearly 30-40 clinical tests in the Aleksandrov National Cancer Center.

However, it is still early to talk about the date for clinical testing of the new method. There is a certain algorithm to follow. It can take up 3 to 4 years from research to the final product.

What are the prospects for the plasmonic nanobubbles technology?
Proceeding from the results of the experiment, we can say it is a small victory over cancer. However, I would like to reiterate that in interpreting our successes we do not go beyond the framework of the experiment. In the future this technology can be used to treat other types of cancer.

How long did the research take? Who financed the studies?
This is a Belarusian-U.S. project launched some three years ago. Dmitry Lapotko, head of laser science at medical nanotechnology group Masimo Corporation, is the leading researcher. The project was financed by Gillson Langenbough Foundation, Houston, TX and the National Science Foundation of the United States.

Thank you for the interview. We wish you every success with this important project.

February, 2016|Oral Cancer News|

Immunotherapies gaining traction in head and neck cancers

Source: www.targetedonc.com
Author: Greg Kennelty

An explosion of immunotherapies is on the horizon for patients with metastatic head and neck cancer, specifically as phase III trials begin to report findings for PD-1 inhibitors. This upcoming wave of new therapies places importance on understanding optimal treatment settings and adverse events associated with these therapies.

In late January, the phase III CheckMate-141 trial investigating the anti–PD-1 agent nivolumab was stopped early, due to a substantial improvement in the primary endpoint of overall survival (OS). The drug was put up against the investigator’s choice of cetuximab (Erbitux), methotrexate, or docetaxel following progression on a platinum-based therapy.

At this time, data from the study have not yet been released but are being prepared for future presentation. Findings from the study are being discussed with the FDA and other health authorities.

In addition to nivolumab, the PD-1 inhibitor pembrolizumab (Keytruda) demonstrated encouraging activity in patients with with advanced PD-L1–positive esophageal carcinoma during the phase Ib KEYNOTE-028 study. Additionally, the agent was effective for patients with squamous cell carcinoma of the head and neck in the phase I KEYNOTE-012 study.

In the head and neck cancer population, the objective response rate with pembrolizumab was 24.8% in 117 evaluable patients. Tumor shrinkage was experienced by 56% of patients and another 25% had stable disease. The response rate seen with pembrolizumab was similar, regardless of HPV infection status. In those with HPV-positive disease, the ORR was 20.6% compared with 27.2% in the negative group.

To gain further insight, Targeted Oncology spoke with head and neck cancer expert Barbara Burtness, MD, professor of Medicine (Medical Oncology), Clinical Research Program Leader, Head and Neck Cancers Program, co-director, Developmental Therapeutics Research Program, Yale Cancer Center.

TARGETED ONCOLOGY: Can you give us an overview of where immunotherapy is currently in head and neck cancer?

BURTNESS: The first trials for immunotherapy in head and neck cancer began two or three years ago and we now have sufficient reason to believe that these therapies are going to be active in the cancer. For example, there is the KEYNOTE-012 trial, which was a trial of pembrolizumab given to an expansion cohort of either HPV-positive or HPV-negative head and neck cancer. The response rate there was about 25%.

There is some reason to believe that if either PD-L1 or PD-L2 are expressed, that that would predict for a higher response rate. There are now phase III trials going forward for both platinum-refractory disease and for first-line patients looking at pembrolizumab compared with chemotherapy.

There are also data with MEDI4736, which if a patient is expressing PD-L1, appears to have a pretty high response rate of about 50% in a small group of patients. There are currently ongoing trials looking at the combination of MEDI4736 with tremelimumab, though we don’t have any data on that just yet.

Then there are novel strategies people have for trying integrate immunotherapy with standard treatment. We have some reason to believe that when head and neck cancer is treated with radiation there is upregulation in tumor-infiltrating lymphocytes and PD-L1. There are trials now moving forward that are integrating immune checkpoint inhibitors together with chemoradiation, or taking patients who have completed their chemoradiation but have persistent disease and exposing them to pembrolizumab in that setting.

The last thing is there is some evidence that siltuximab can upregulate a co-stimulatory molecule, CD137. There are some trials looking at co-targeting EGFR and CD137.

TARGETED ONCOLOGY: What are the side effects in immunotherapy?

BURTNESS: The one thing community oncologists should be aware of is toxicities. As these drugs roll out, these toxicities that will be present are a lot different to manage than the usual cytotoxic agent toxicities. There are a lot of unusual or unexpected side effects that are autoimmune in nature.

The most common toxicity is fatigue. Across all the patients with head and neck cancer who received pembrolizumab, about 17% of them had grade 3 or 4 toxicities. This is a lot easier to tolerate than chemotherapy or chemoradiation. The other things that you might look for are pneumonitis, nephritis, pancreatitis with diabetic symptoms, thyroiditis, and a variety of unusual autoimmune side effects.

TARGETED ONCOLOGY: What do you see as the overall potential for immunotherapy in head and neck cancer?

BURTNESS: Everybody with biomarker expression of either the ligands or the targets in this pathway is likely to be exposed to these drugs in the future. The challenge for us is going to be to figure out, for those patients who are not PD-L1 expressing or who don’t have tumor-infiltrating lymphocytes, other ways that we can prime patients for immunotherapy with our standard treatments. It’s speculative – it’s not something that people are doing in clinics now, but the first trials of those approaches are starting.

There is also ADXS11-001 that is fused to the E7 oncogene from HPV. The idea is that that would increase antigenic presentation and then the immune checkpoint inhibitor could potentially be more effective. That treatment is still in phase I.

February, 2016|Oral Cancer News|

Oral cancer less likely in women who have more sex; but not the same for men

Source: www.parentherald.com
Author: Diane Ting

Having more sex partners reduces the chance of oral cancer for women. Unfortunately, men are more likely to become infected as the number of oral sex partners increases.

A study suggests that women who have more vaginal sex partners appear to have a lower risk of oral human papillomavirus (HPV) infections. The information was released during the annual conference of the American Association for the Advancement of Science. Throat and mouth cancer are linked to HPV, which is one of the most prevalent sexually transmitted diseases. HPV is rather common, as most people are treated of the virus within two years.

According to the study published by the Journal of the American Medical Association (JAMA), oral sex may increase the risk of head and neck cancer by 22 percent. In the last 20 years, the number of oral cancer patients has risen to 225 percent.

Oral cancer is typically linked to lifestyle causes such as heavy drinking and smoking, according to Mirror. Two in three sufferers of oral cancer were men, which made experts question the imbalance.

HPV is the same cancer that causes cervical cancer in women. Research states that because women are first exposed to HPV vaginally, they may develop an immune response that prevents them from getting the infection.

Unfortunately, research suggests that this may not be the same for men as they are found twice more likely to develop oral cancer. As the number of oral sex partners increase, the risk of oral HPV infections also increases. It is believed that oral sex may be the main cause at which the HPV ends up in the mouth. “Our research shows that once you become infected, men are less likely to clear this infection than women, further contributing for the cancer risk,” according to Gypsyamber D’Souza, a professor at Johns Hopkins University in Baltimore.

Oral sex can dramatically increase a person’s risk of the common human papillomavirus (HPV) by 22 times, which can eventually lead to cancer, according to a study. While HPV is very common and easily treatable, HPV may not go away in some cases particularly with men. In some rare instances, the virus can lead to cellular changes in the mouth and throat, which can lead to cancer.

Middle-aged white men are particularly at high risk compared to other races, according to Daily Mail. The US Centers for Diseases Control and Prevention (CDC) has highly recommended all pre-teenagers to take the HPV vaccination before they become sexually active.

February, 2016|Oral Cancer News|

HPV vaccination rates are low, especially in Kansas and Missouri, and cancer experts are alarmed

Source: www.kansascity.com
Author: Lisa Gutierrez
HPV (2)The HPV vaccine is recommended for girls and boys starting at ages 11 to 12. But in state-by-state comparisons, children in Kansas and Missouri rank at or near the bottom of the list. John Amis The Associated Press

 

The University of Kansas Cancer Center recently joined nearly 70 other cancer centers across the country to sound an alarm about the HPV vaccine.

Many children still are not getting the recommended vaccine for human papillomavirus, which causes head and neck cancer in men and women, cervical cancer in women and a host of other cancers in both.

In Kansas and Missouri, less than 49 percent of girls have received the vaccine, according to the Centers for Disease Control and Prevention. Kansas ranks dead last in the nation, and Missouri is near the bottom. Both states rank low for the number of boys who are vaccinated too.

The public call from KU’s cancer center was blunt: The vaccine prevents cancer. What’s the problem?

“It absolutely breaks my heart,” said Terry Tsue, physician-in-chief at the University of Kansas Cancer Center. “We have two vaccines against cancers that are caused by virus, the hepatitis A vaccine and the HPV vaccine. Otherwise, we don’t have a vaccine that prevents cancer.

“There are thousands and thousands of people dying annually from this disease that could have been prevented had we had this vaccine 30 years ago. We didn’t have it and were so slow in adopting it that for the next 30 years we’re going to lose the same number of people, and more, because it’s spreading.”

The nation’s cancer centers banding together to issue a collective statement was a rare move for those involved in cancer research and prevention.

The low HPV vaccination numbers represent a public health threat, said cancer center officials, who asked health care providers and parents to take advantage of the vaccine.

Considering President Barack Obama’s new “moonshot” efforts to cure cancer, “this is one example of actions that can be taken today to make a very big difference in the future cancer burden,” said a statement from Ernest Hawk, vice president and division head of cancer prevention and population sciences at the University of Texas MD Anderson Cancer Center.

Tsue is stunned by what people don’t know about HPV. For instance, about 70 percent of parents apparently don’t know that the vaccine is recommended for boys as well as girls.

The vaccine not only prevents “female” cancers — cervical, vaginal, vulvar — but it also prevents cancer in the throat, known as oropharyngeal cancers. And three times as many men as women get throat cancer from HPV, says Tsue.

Twenty percent of patients with HPV-related throat cancers die within five years.

“Our practitioners aren’t aware of the magnitude and this kind of tsunami of cases,” said Tsue, a head and neck surgeon. “Throat cancer related to HPV is growing up to 5 percent a year. No other cancer is growing like that. And it will surpass cervical cancer caused by HPV by 2020.”

According to the CDC, HPV infections are responsible for about 27,000 new cancer diagnoses each year in the U.S.

So the CDC recommends that all boys and girls get a three-dose round of HPV vaccine shots at the ages of 11 or 12. The vaccine can be up to 93 percent effective when it’s given at that optimal time, CDC officials say.

But vaccination rates are low. The U.S. Department of Health and Human Services set a goal to have 80 percent of American girls ages 13 to 15 fully vaccinated by the year 2020. But four out of 10 girls remain unvaccinated, according to CDC statistics, and fewer than six out of 10 boys have been vaccinated.

Tsue says that health professionals are battling a lot of misinformation and misconception among the public. Surveys of parents, for instance, show that many mistakenly think HPV has something to do with HIV.

Tsue thinks another issue is that parents equate the vaccine with sex because the virus is most commonly sexually transmitted, though it can sometimes be transmitted without sexual contact.

Parents tells survey takers that their children don’t need the vaccine because their kids aren’t having sex.

However, most men and women in the United States will be infected with at least one type of HPV at some time in their lives.

“Eighty percent of adults get HPV in their lives — 80,” said Tsue. “So this isn’t for the hooker on the corner of the red light district. This is 80 percent of the U.S. population will have HPV sometime in their life.”

Tsue thinks that some parents also believe that having their children vaccinated will somehow give them free rein to have sex or will promote promiscuity, though studies have shown that getting the vaccine doesn’t make kids more likely to have sex at a younger age.

“So your 10-year-old who has no idea what the shot they’re getting is will subsequently go out and have sex the next week because they got a shot that prevents the HPV virus?” said Tsue. “That’s (what) we’re dealing with.”

Though the vaccine is not known to cause serious or long-term side effects, questions about its safety linger for some parents, particularly those who have sworn off childhood vaccines. Five years ago, then-congresswoman Michele Bachmann of Minnesota charged during a presidential debate that the vaccine was “very dangerous” and caused “mental retardation.”

A study published in Pediatrics in 2013 showed that among the most frequent reasons parents gave for not having their children vaccinated was fear of the vaccine’s safety.

The website VacTruth.com — run by a father who says his son was harmed by childhood vaccinations — published a story last month charging that reports of serious side effects and deaths linked to HPV vaccines are being kept secret from the public.

Thousands of young girls, the story claims, “have fallen seriously ill, have had their health completely ruined after these vaccines and many have died.”

It cited records from the website Judicial Watch, which describes itself as “a conservative, nonpartisan educational foundation,” claiming that one of the HPV vaccines, Gardasil, is linked to “thousands of serious adverse reactions and debilitating side effects, including seizures, blindness, paralysis and dozens of deaths.”

Judicial Watch, which has been investigating the vaccine for the last few years, has dubbed the HPV vaccine “a large-scale public health experiment.”

The medical community considers the vaccine one of the safest around.

“All this bad press about vaccines, how it kills people, how it causes autism, all false,” said Tsue.

Tsue talks to small groups of health care professionals about HPV-related cancers on his quest to promote the vaccine. He believes that more pediatricians and family practitioners should start talking to parents about it too.

“We need to help providers to make a strong cancer prevention recommendation for vaccinating 11- and 12-year-old boys and girls with the HPV vaccine,” Anna Giuliano, director of the Center for Infection Research in Cancer at Moffitt Cancer Center in Tampa, Fla., told NPR earlier this month.

“If all the pediatricians and family practice doctors were making that strong recommendation, I think we would see a strong increase in the rate of uptake in that vaccine.”

Tsue and other cancer experts would like to see the HPV vaccine added to the lineup of regularly scheduled vaccines schoolchildren already receive: tetanus, diphtheria, whooping cough and meningitis, among them.

Tsue supports mandatory vaccination too — neither Kansas nor Missouri mandates the vaccine — but that’s been a hard sell already.

In 2011, Gov. Rick Perry of Texas had to reverse his decision to make the vaccine mandatory when conservative parents in his state revolted.

The Rhode Island General Assembly faced the same objections last year after it required the vaccine for all seventh-graders. The Rhode Island Center for Freedom & Prosperity held a rally protesting the mandate on the vaccine with parents who said their children got sick from it.

Parents also argue that they should be allowed to make the vaccination decision themselves, a point that the American Civil Liberties Union supports Rhode Island parents on.

Meanwhile, public health officials in Massachusetts itching to do something to raise the rate of HPV vaccinations there are watching Rhode Island’s success with the mandate, according to The Boston Globe.

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

February, 2016|Oral Cancer News|