Oral Cancer News

Fighting cancer in the pandemic means fighting cancer alone

Source: The Washington Post
Date: August 12, 2020
Author: Laura B. Kadetsky

 

A doctor pointed out to me at a recent appointment that my latest bout with oral cancer tracked the first spikes of the coronavirus pandemic. On that beautiful, cancer-free day in late May, workers chatted over lunch outside the hospital entrance, and I gawked at their carefree togetherness while I hurried by wearing my mask and gloves. It was a world apart from March, when I hastily scheduled a biopsy in case the hospital canceled ENT procedures entirely, and April, when I had the surgery in an abnormally quiet hospital, where coronavirus precautions were expanding daily.

In March, horror stories were flooding in, and the threat of the virus hung over everything. Waiting for the biopsy results only heightened that pandemic-induced anxiety: How do you deal with cancer when no one knows what’s safe anymore? Although it felt like the pandemic put most of life on hold, serious health issues don’t wait for a worldwide crisis to end. After I had spent 10 years fighting oral cancer on and off, the cancer was back, and I had to deal with it.

At the hospital, which already had covid-19 patients, the danger of infection seemed everywhere. I focused on ways to try to control my risk — maybe because having cancer makes everything else feel squarely out of control. I parked on the street to avoid having a stranger park my car in the hospital garage and contaminate it. I wore my homemade dish-towel mask, because masks hadn’t yet become widely available. I covered the driver’s seat with a sheet in case my clothes picked up the virus and transferred it to the car, as this was before we learned more about surface transmission. Those things won’t stop cancer, I reasoned, but maybe they’d block the virus.

Walking the halls, I kept my eyes down to avoid sending — or receiving — accusatory looks: Did you cough near me? Why are you in the hospital? Do you have the virus? I tallied door handles: three to get in and out of the building, each one a potential germ site. It felt bizarre to be this hyper-alert and yet entirely reasonable.

I needed a coronavirus test before the surgery, well before drive-through testing sites popped up. As much as I feared getting the virus, the medical workers rightly worried that they might get it from me. In ENT surgeries especially, working in or near the respiratory system risks the virus spreading throughout the operating room. I understood, but I obsessed about it. It sounded barbaric, adding insult to injury: I already have cancer, and now you have to jam a cotton swab up my nose, too?

In good-for-coronavirus news, the test was negative, and surgery was on — and at the start of Oral, Head and Neck Cancer Awareness Week, no less (a reminder: I don’t smoke, and I rarely drink alcohol, so everyone thinking this happens to “someone else” should have their oral cancer screening as soon as they can get to the dentist). Having been through this before, my husband and I thought we knew how to get ready. But preparing for surgery in a pandemic comes with new complications. With quarantines and the dangers of infection for our elderly parents, no family members could come to help. Physical distancing norms left us worried about asking friends for anything. I’d been having groceries delivered for years, but suddenly, I couldn’t get a slot. I found myself staying awake for hours refreshing the overwhelmed delivery website in the middle of the night, funneling my stress into obsession about how to feed my family safely and find food I could eat after surgery.

We agonized about how to tell our 5-year-old son. The anxiety of the pandemic had ratcheted up my distraction, and I’d been mixing up words for weeks. I tried to explain bandages to him and compared them to zombies. “No, Mommy,” he corrected me, giggling, “you’ll be a mummy, not a zombie.” Of course, he was right. He decided I needed one of his stuffed animals to take with me. In the face of his generosity, I hesitated, wondering how we could clean germs off a stuffed giraffe.

Between the placement of the tumor, and the multiple prior surgeries, I faced an uncertain outcome. Only after surgery started would we find out how intense it would be. No matter what, though, I would be staying in the hospital, where covid-19 numbers were increasing daily. All the controls I’d put in place to stay safe were gone. Although I was tested, the medical staff was not all tested before touching me — let alone operating on me. I couldn’t wash my hands while sedated or wear a mask during the surgery. No one wants to stay in the hospital, but now I was bucking all the directives; not only would people not be six feet away, they would actually have their hands in my mouth and all over my face. Everything I had been told not to do was turned on its head.

And no matter what, I would be alone. Because of the coronavirus, my family was barred from visiting me in the hospital. The doctors suggested that my husband not stay in the surgical waiting room, or anywhere on the hospital campus, to find out what happened, in case anyone there carried it (although in the end, he refused to leave until the procedure was done). When they wheeled me out of pre-op, we didn’t know when we would see each other again or in what condition I would be. I couldn’t comprehend how I would manage on my own. He couldn’t comprehend not being there for me.

When we are sick, those closest to us provide a vital source of healing. Yet the pandemic makes that physically impossible. When I was hospitalized, the distance between my family and friends and me was not just six feet, but absolute. My family couldn’t act on a basic human need to provide comfort through their presence. Instead, my son made colorful, glittery drawings, and my husband covered them with cheering messages, such as, “Sending you healing powers from your #1 fans.” But notes and video calls can’t replace someone at your bedside. It is a terrible loss when those of us at our most vulnerable cannot be fully present with those who love us most; the pandemic exacerbates patients’ suffering by making that impossible.

In one version of this story, I was lucky. My surgery was one of the serious cases still allowed to proceed when many hospitals had been turned into covid wards (shortly after waking up, I overheard someone tell another patient, “Congratulations, you have a new kidney!”). The surgeons and medical staff worked magic, and I made it through the surgery with the best possible outcome. I had access to a hospital system that saw what happened in New York and prepared before cases rose, so the medical staff caring for both me and the covid patients there knew how to stay protected.

But in the other version, being a patient right now is a nightmare. It means having to ask things such as, “Will a ventilator be available if I need it?” “Will the hospital allow my care to proceed?” “How will my husband take me to the hospital when our son is at home with no child care?” “How will I get through this alone?” Or, “When I can’t speak post-surgery and am alone in the hospital, when I can’t advocate for myself, who will advocate for me?”

People are desperate to be done with restrictions; I get it. They’re tired of being stuck at home. They want to hang out with their friends without worrying about killing them. But the virus is still out there. And the longer we let it linger, the more people will have to go through what I went through.

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August, 2020|Oral Cancer News|

Doctors diagnose advanced cancer—in a dinosaur

Source: Science Mag
Date: August 3rd, 2020
Author: Gretchen Vogel

 

This deformed bone is the first clear example of a malignant tumor diagnosed in a dinosaur. The partial fibula—a bone from the lower leg—belonged to a horned, plant-eating Centrosaurus that lived roughly 76 million years ago in what is now Dinosaur Park in southern Alberta in Canada.

Paleontologists initially thought the bone’s strange shape was due to a fracture that hadn’t healed cleanly. But a new study, published today in The Lancet Oncology, compares the internal structure of the fossil (above) with a bone tumor from a human patient to seek a diagnosis. The conclusion: The dinosaur suffered from osteosarcoma, a cancer that, in humans, primarily attacks teens and young adults. The disease causes tumors of immature bone tissue, frequently in the long bones of the leg.

This isn’t the first time cancer has been found in fossil remains. Scientists have identified benign tumors in Tyrannosaurus rex fossils and arthritis in duck-billed hadrosaurs, as well as an osteosarcoma in a 240-million-year-old turtle. But the researchers say their study is the first to confirm a dinosaur cancer diagnosis at the cellular level.

Scientists, including paleontologists, pathologists, a surgeon, and a radiologist, examined the full fossil with high-resolution computerized tomography scans and examined thin sections under the microscope to evaluate the structure of the cells. They found that the tumor was advanced enough that it had probably plagued the animal for some time. A similar case in a human, left untreated, would likely be fatal, they write. However, because the fossil was found in a bone bed with lots of other Centrosaurus specimens, the dinosaur likely died in a flood with the rest of its herd and not from the cancer.

The researchers say their diagnosis shows a more careful look at unusual fossil malformations using modern imaging and diagnostic techniques can pay off, leading to new insights about the evolutionary origins of diseases.

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August, 2020|Oral Cancer News|

JOMS study: For jaw cancer patients, in-house 3D printing allows quicker restoration of teeth

Source: www.prnewswire.com/
Author: News provided by Journal of Oral and Maxillofacial Surgery

In-house 3D printing allows patients with malignant disease to more quickly receive immediate tooth restoration – treatment that had been regarded as of low importance for these patients due to the severity of their disease, a new study found.

The 3D digital workflow eliminates the wait in providing replacement teeth using the conventional approach and is less costly, according to the study published in the August issue of the Journal of Oral and Maxillofacial Surgery, the official journal of the American Association of Oral and Maxillofacial Surgeons (AAOMS).

For the study, 12 patients underwent virtual surgical planning (VSP) for a procedure called free fibula maxillofacial reconstruction, which replaces bone and soft tissues in the face removed to treat cancer with bone and soft tissue from the patient’s leg. A dental prosthesis was created for each patient to be placed at reconstruction. For five patients, a dental laboratory made the prostheses. For the other patients, a surgeon designed the prostheses and 3D printed them in-house. Four of the patients who received a prosthesis from the in-house 3D printing had malignant tumors.

Researchers found time and cost were less for developing the prostheses in-house than using a dental laboratory. Sending production of a prosthesis to dental laboratories leads to delays in the prosthesis being ready to give to the patient soon after cancer surgery, the study notes.

“Such a delay has limited the usefulness of this treatment to benign conditions,” researchers wrote. “With point-of-care 3D printing, we have fabricated a dental prosthesis within 24 hours of the VSP session, eliminating any additional waiting period before surgery.”

For the in-house printing, the surgeon received digital files immediately after the VSP session. Within a day, the prosthesis was 3D printed. The in-house prostheses were prepared for surgery one to two weeks before a plate and models from VSP arrived, so treatment was not delayed more than the standard duration for acquiring the plate and models from the vendor, according to the study.

By comparison, the offsite dental laboratory needed an additional two weeks to create the prostheses. On average, the prostheses created at the offsite dental laboratory cost $617 compared to $8.34 for resin for the in-house 3D prosthesis, the study notes. However, the researchers cautioned that costs are associated with obtaining a 3D printer and supplies (less than $3,000).

The small study did not compare prosthesis quality between the two settings.

“As point-of-care 3D printing becomes available to more surgeons, we anticipate this will become a viable solution for many patients,” researchers wrote.

The authors of “Immediate Teeth in Fibulas: Planning and Digital Workflow With Point-of-Care 3D Printing” are Fayette C. Williams, DDS, MD; Daniel A. Hammer, DDS; Todd R. Wentland, DDS, MD; and Roderick Y. Kim, DDS, MD; from the Division of Maxillofacial Oncology and Reconstructive Surgery at John Peter Smith Health Network in Fort Worth, Texas.

The full article can be accessed here.

The Journal of Oral and Maxillofacial Surgery is published by the American Association of Oral and Maxillofacial Surgeons to present to the dental and medical communities comprehensive coverage of new techniques, important developments and innovative ideas in oral and maxillofacial surgery. Practice-applicable articles help develop the methods used to handle dentoalveolar surgery, facial injuries and deformities, TMJ disorders, oral and head and neck cancer, jaw reconstruction, anesthesia and analgesia. The journal also includes specifics on new instruments and diagnostic equipment, and modern therapeutic drugs and devices.

Source: Journal of Oral and Maxillofacial Surgery

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August, 2020|Oral Cancer News|

Immunotherapy-resistant cancers eliminated in mouse study

Source: Science Magazine
Date: August 11th, 2020
Author/Credit: William Vermi/Martina Molgora

Immunotherapy has revolutionized cancer treatment by stimulating the patient’s own immune system to attack cancer cells, yielding remarkably quick and complete remission in some cases. But such drugs work for less than a quarter of patients because tumors are notoriously adept at evading immune assault.

A new study in mice by researchers at Washington University School of Medicine in St. Louis has shown that the effects of a standard immunotherapy drug can be enhanced by blocking the protein TREM2, resulting in complete elimination of tumors. The findings, which are published Aug. 11 in the journal Cell, point to a potential new way to unlock the power of immunotherapy for more cancer patients.

“Essentially, we have found a new tool to enhance tumor immunotherapy,” said senior author Marco Colonna, MD, the Robert Rock Belliveau, MD, Professor of Pathology. “An antibody against TREM2 alone reduces the growth of certain tumors, and when we combine it with an immunotherapy drug, we see total rejection of the tumor. The nice thing is that some anti-TREM2 antibodies are already in clinical trials for another disease. We have to do more work in animal models to verify these results, but if those work, we’d be able to move into clinical trials fairly easily because there are already a number of antibodies available.”

T cells, a kind of immune cell, have the ability to detect and destroy tumor cells. To survive, tumors create a suppressive immune environment in and around themselves that keeps T cells subdued. A type of immunotherapy known as checkpoint inhibition wakes T cells from their quiescence so they can begin attacking the tumor. But if the tumor environment is still immunosuppressive, checkpoint inhibition alone may not be enough to eliminate the tumor.

An expert on the immune system, Colonna has long studied a protein called TREM2 in the context of Alzheimer’s disease, where it is associated with underperforming immune cells in the brain. Colonna and first author Martina Molgora, PhD, a postdoctoral researcher, realized that the same kind of immune cells, known as macrophages, also were found in tumors, where they produce TREM2 and promote an environment that suppresses the activity of T cells.

“When we looked at where TREM2 is found in the body, we found that it is expressed at high levels inside the tumor and not outside of the tumor,” Colonna said. “So it’s actually an ideal target, because if you engage TREM2, you’ll have little effect on peripheral tissue.”

Colonna and Molgora — along with colleagues Robert D. Schreiber, PhD, the Andrew M. and Jane M. Bursky Distinguished Professor; and William Vermi, MD, an immunologist at the University of Brescia — set out to determine whether inhibiting TREM2 could reduce immunosuppression and boost the tumor-killing powers of T cells.

As part of this study, the researchers injected cancerous cells into mice to induce the development of a sarcoma. The mice were divided into four groups. In one group, the mice received an antibody that blocked TREM2; in another group, a checkpoint inhibitor; in the third group, both; and the fourth group, placebo. In the mice that received only placebo, the sarcomas grew steadily. In the mice that received the TREM2 antibody or the checkpoint inhibitor alone, the tumors grew more slowly and plateaued or, in a few cases, disappeared. But all of the mice that received both antibodies rejected the tumors completely. The researchers repeated the experiment using a colorectal cancer cell line with similarly impressive results.

With the help of graduate student Ekaterina Esaulova, who works in the lab of Maxim Artyomov, PhD, an associate professor of pathology and immunology, the researchers analyzed immune cells in the tumors of the mice treated with the TREM2 antibody alone. They found that suppressive macrophages were largely missing and that T cells were plentiful and active, indicating that blocking TREM2 is an effective means of boosting anti-tumor T cell activity.

Further experiments revealed that macrophages with TREM2 are found in many kinds of cancers. To assess the relationship between TREM2 expression and clinical outcomes, the researchers turned to The Cancer Genome Atlas, a publicly available database of cancer genetics jointly maintained by the National Cancer Institute and the National Human Genome Research Institute. They found that higher levels of TREM2 correlated with shorter survival in both colorectal cancer and breast cancer.

The researchers are now expanding their study of TREM2 to other kinds of cancers to see whether TREM2 inhibition is a promising strategy for a range of cancers.

“We saw that TREM2 is expressed on over 200 cases of human cancers and different subtypes, but we have only tested models of the colon, sarcoma and breast, so there are other models to test,” Molgora said. “And then we also have a mouse model with a human version of TREM2.”

Added Colonna: “The next step is to do the animal model using the human antibody. And then if that works, we’d be ready, I think, to go into a clinical trial.”

 

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August, 2020|Oral Cancer News|

Most parents of unvaccinated teens have no intention of getting HPV vaccine for their kids, study finds

Source: www.newstribune.com
Author: Kasra Zarei, The Philadelphia Inquirer

The human papillomavirus (HPV) vaccine has been proven to prevent certain types of oral and genital cancers and other health problems. However, in a study published this week in Lancet Public Health, researchers found that more than half of the parents of adolescents who have not received the HPV vaccine had no intention to initiate the vaccine series for their children.

Using data from a nationally representative survey of U.S. adolescents, the study authors estimated national-level and state-level parental intent to initiate and complete the HPV vaccine series for their kids. In states including Idaho, Montana, Nebraska, North Dakota, Oklahoma, and Utah, more than 65 percent of parents of unvaccinated adolescents had no intention to initiate the HPV vaccine series.

According to the most recent data by the Centers for Disease Control and Prevention, Wyoming and Mississippi have the lowest HPV vaccine rates at roughly 50 percent. The new study found of parents of unvaccinated adolescents in these states, almost 62 percent and 57 percent, respectively, did not intend to initiate the HPV vaccine for them.

Lack of parental intent to complete the vaccine series was lowest in the District of Columbia, at nearly 11 percent, and Rhode Island, at 20 percent. HPV vaccination is mandated in both regions.

In Philadelphia, HPV vaccine coverage is among the highest in the country — roughly 71 percent in 2018, according to CDC data. Still, in Pennsylvania, between 60-65 percent of the parents of unvaccinated adolescents do not intend to have their kids start the vaccine.

“I was surprised that the intent to vaccinate (for HPV) is this low,” said Cynthia DeMuth, a primary-care pediatrician in Harrisburg and the Pennsylvania chapter immunization representative for the American Academy of Pediatrics, who was not involved with the study.

The HPV vaccine guidelines recommend adolescents who start the vaccine series before their 15th birthday receive two doses, or three doses if they start after their 15th birthday.

But even among kids who receive the first dose, many parents don’t intend to have their child complete the series, the study found. Nationally, almost a quarter of the parents of adolescents who received the first dose of the vaccine had no intention to complete the series. In states like Arkansas, Florida, Georgia, Hawaii, Idaho, Utah, and West Virginia, that percentage was even higher at more than 30 percent.

Research suggests parents’ main driver is perceived safety of the vaccine, which may be due to past reports of adverse effects since the vaccine’s approval in 2006.

“It’s a safe and effective vaccine, and there haven’t been any serious adverse events related to the vaccine,” DeMuth said.

Studies have since proven rates of cancers that are prevented by the HPV vaccine have greatly decreased. Experts estimate widespread HPV vaccination has the potential to reduce new cervical cancer cases around the world by as much as 90 percent.

Lack of knowledge about the vaccine and lack of recommendations from health-care providers are also reasons expressed by parents with no intent to vaccinate their kids.

“Adults between the ages of 18 to 45 don’t even know what HPV is, and there is a vaccine to protect it,” said Kalyani Sonawane, professor in the department of management, policy, and community health at the University of Texas Health Science Center and lead author of the study.

There are also perceptions the vaccine is not needed for younger teens who may not be sexually active, as HPV is mainly sexually transmitted.

When declining the HPV vaccine, “sometimes parents say their child is too young and isn’t sexually active, and they’ll think about it for next year,” DeMuth said. “But the vaccine works better at young ages — the antibody levels are higher at a younger age with two shots compared to three shots at older ages.”

These trends worry experts who say it could cause a rise in HPV-related cancer rates.

“Particularly among girls, the coverage rate has not improved. If parents are not intending to vaccinate their kids, in the future, we could expect to see an increase in HPV-associated cancers,” Sonawane said.

Sonawane said while people may not think about HPV like measles, for which low vaccine coverage can lead to outbreaks, HPV is still an infectious disease and can remain in the body for years. HPV-related cancers are already on the rise by almost 3 percent. Experts caution if vaccine coverage doesn’t improve, increases in HPV-related cancers are only going to get worse.

Health care professionals and pediatricians can play an immediate role in addressing these potential health concerns.

“A strong recommendation from the provider is one of the most significant things providers can do,” DeMuth said. “The longer it’s been out, the more confident I am it’s safe, and the better I feel about giving a strong recommendation for the vaccine.”

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August, 2020|Oral Cancer News|

Standard therapy prevails in head & neck cancer trial

Source: www.medpagetoday.com
Author: Charles Bankhead, Senior Editor, MedPage Today

Neither a single immune checkpoint inhibitor nor a combination improved survival versus standard of care for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), an international randomized trial showed.

Durvalumab (Imfinzi) alone led to a media overall survival (OS) of 7.6 months, and patients treated with the combination of durvalumab and tremelimumab had a median OS of 6.5 months. Both values were numerically lower than the 8.3-month median achieved with standard therapy, according to Robert L. Ferris, MD, of the University of Pittsburgh Hillman Cancer Center, and colleagues.

In landmark analyses, both single-agent durvalumab led to numerically higher OS at 12, 18, and 24 months, and the combination had higher OS at 18 and 24 months. None of the differences achieved statistical significance versus standard of care, they reported in the Annals of Oncology.

“Despite the apparent lack of benefit over standard of care, durvalumab clinical activity was in line with other checkpoint blockade agents in this setting,” they wrote. “Although cross-trial comparisons should be approached with caution, median OS for durvalumab was similar to median OS for nivolumab (Opdivo) and pembrolizumab (Keytruda) in comparable patient populations. Likewise, 12-month survival rates for all three were similar.”

“This study was characterized by an unexpectedly high OS for the standard-of-care arm, with a median of 8.3 months,” the authors continued. “This outcome was higher than median OS values for standard-of-care arms reported in similar studies with PD-1 inhibitors.”

Ongoing biomarker studies may provide insight into the clinical activity of immune checkpoint inhibition in HNSCC, they added.

The rationale for the EAGLE trial included evidence from studies of other tumor types showing enhanced additive activity with the combination of a PD-1/L1 inhibitor with a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor. The evidence included studies of durvalumab and tremelimumab in other solid tumors, Ferris and colleagues noted. Moreover, single-agent durvalumab demonstrated activity in previous studies of relapsed/metastatic HNSCC.

Investigators at 156 sites around the world enrolled patients with HNSCC that progressed during or after treatment with a platinum-based regimens. Patients were randomized to one of three treatment groups: durvalumab alone, durvalumab plus tremelimumab, or a standard-of-care single-agent therapy (such as cetuximab [Erbitux], a taxane, or methotrexate). The primary endpoint was OS.

The primary analysis included 736 randomized patients. The results showed no significant difference in the survival hazard ratio (HR) versus standard of care for single-agent durvalumab (HR 0.88, 95% CI 0.72-1.08) or the combination (HR 1.04, 95% CI 0.85-1.26).

The 12-month OS numerically favored durvalumab (37.0% vs 30.5% for standard of care), whereas the combination arm had a 12-month OS almost identical to that of the control arm (30.4% vs 30.5%). Analysis of 24-month survival showed numerical advantages favoring both experimental arms (18.4% for durvalumab, 13.3% for the combination, 10.3% for standard of care). The trial was not designed or statistically powered to compare the durvalumab and combination arms.

Multiple factors might explain the “disappointing” results of the trial, wrote Marco Carlo Merlano, MD, of Candiolo Cancer Center in Torino, Italy, in an accompanying editorial. In a previous study of pembrolizumab, a fourth of patients had PD-L1 expression ≥50. In the current study, 28% of patients had PD-L1 expression ≥25%.

“Therefore, we can speculate that the population that benefits most by the anti-PD-L1 durvalumab therapy is less represented in this study, reducing the overall benefit of the drug,” said Merlano, who also questioned the accuracy and reliability of the methodology used to determine PD-L1 staining in the trial.

A strong theoretical rationale exists for combining a PD-L1 inhibitor and a CTLA-4 inhibitor in HNSCC. However, functional or physical elimination of regional lymph nodes during surgery or radiation therapy for HNSCC might reduce CTLA-4 inhibition in the disease, Merlano continued.

Although ipilimumab (Yervoy) and tremelimumab both target CTLA-4, the antibodies have structural differences that leave tremelimumab unable to induce antibody-dependent cell cytotoxicity. An additional potential consideration is the reduced CTLA-4 expression by natural killer (NK) cells, which are the most common type of T-cells found in the HNSCC microenvironment.

Merlano cited imbalances potentially favoring the standard-of-care arm in the multivariable analysis. He insisted that, in the absence of direct comparisons, there could be differences in the potency of PD-1 inhibitors (such as nivolumab and pembrolizumab) versus PD-L1 inhibitors (such as durvalumab).

“However, regardless of the result of anti-PD-(L)1/CTLA-4 combinations in HNSCC, combinations of immunotherapy or combinations of immunotherapy and conventional therapies are the most promising approaches to solid tumors,” Merlano concluded.

Author: Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology.

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Common causes of dysphagia in seniors may differ by sex, study finds

Source: www.mcknights.com
Author: Alicia Lasek

Common causes of swallowing problems may differ significantly between older men and women, according to physician researchers.

In a two-year swallowing clinic study, neuromuscular and esophageal problems were the most frequent causes of dysphagia among 109 study participants, reported Jeremy Applebaum, M.D., from Johns Hopkins University. Many patients (16%) had either diverticula (a soft pouch in the esophagus that can collect food particles), reflux (14%) or scarring caused by radiation treatment (8%). These problems also were associated with significant quality-of-life burden, the researchers added.

Causal differences were also found between the sexes. Men were more likely to have oropharyngeal dysphagia, a difficulty with initiating swallowing as food is introduced to the pharynx and esophagus from the mouth. In contrast, women were more likely to present with esophageal dysphagia, which can have several causes and is typically associated with the sensation of food sticking in the throat or chest after starting to swallow.

Higher rates of smoking and head and neck cancer may explain the prevalence of oropharyngeal problems found in male participants, whereas the esophageal problems in women likely were due to the high prevalence of reflux disease among that cohort, the authors surmised. They did not find significant differences in cause between older age cohorts.

Up to 33% of people age 65 and older are known to have swallowing problems due to physical changes, yet dysphasia also may be the result of underlying disease, the investigators said.

“A complaint of dysphagia in older adults should therefore be regarded as pathologic, especially given the wide spectrum of neuromuscular and structural disorders that increase in prevalence with age,” wrote Applebaum and colleagues. “We hope to inform more nuanced, patient-based approaches to this increasingly important topic,” they concluded.

The study was published in OTO Open: The Official Open Access Journal of the American Academy of Otolaryngology–Head and Neck Surgery Foundation.

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Researchers take head and neck cancer by the throat

Source: www.brisbanetimes.com.au
Author: Stuart Layt

Research has identified more weak spots in a deadly type of head and neck cancer that it is hoped will lead to more effective treatments.

Oropharyngeal cancer can affect the base of the tongue, the tonsils, soft palate and parts of the throat, and almost half of all cases in Australia are caused by the human papillomavirus (HPV).

Current immunotherapies target two protein receptors on the cancer; however, they have had mixed success.

Lead researcher Professor Rajiv Khanna from QIMR Berghofer said they had identified four more spots on the genome of the cancer that they believed could be targeted by immunotherapy.

“Everybody has been trying to make immunotherapies that target those two antigens, but what we have found is that while those two are important, we were ignoring some of the other antigens,” Professor Khanna said.

“We took immune cells out of our patients and effectively asked them what they could “see” other than [the two proteins] E6 and E7, and actually they could see others.”

The study analysed immune cells taken from 66 oropharyngeal cancer patients at the Royal Brisbane and Women’s Hospital and the Princess Alexandra Hospital.

Co-lead author Professor Sandro Porceddu, the director of radiation oncology research at the Princess Alexandra Hospital, said they were now developing therapies based on the research.

“We’re already working on developing better killer T-cell immunotherapies that recognise all, or a combination, of these proteins,” Professor Porceddu said.

“Different combinations of the proteins are present on different patients’ cancer cells, so we will develop immunotherapies with different bunches of keys for different patients.”

At present, the cancer is treated with a combination of chemotherapy and radiation therapy, but it is hoped an effective immunotherapy will eventually become the standard treatment.

Oropharyngeal cancers are the sixth-most-common type of cancer worldwide, with US actor Michael Douglas diagnosed with stage four oral cancer in 2010, before going into remission after aggressive radiation treatment and chemotherapy.

Douglas credited HPV for his cancer but later said he was a heavy smoker and drinker, habits that also increase the risk of developing the disease.

In Queensland the incidence rate for the cancer type has increased by 162 per cent in men and 40 per cent in women over a 15-year period, according to data from the Cancer Alliance Queensland.

That is despite the development of the HPV vaccine from Professor Ian Frazer and his team at the University of Queensland in the early 2000s.

However, experts warn the impact of widespread immunisation programs for HPV will not be felt for decades.

The research has been published in the Journal of Experimental Medicine.

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Towards the early detection of oral cancers

Source: pursuit.unimelb.edu.au
Authors: Dr Tami Yap and Professor Michael McCullough, University of Melbourne

If you noticed a new dark spot on your shoulder or changes in an old mole – you would know to get it checked out.

But would you know if you had a skin cancer in your mouth?

As our population ages, the diagnosis of oral cancer is increasing. Globally, this devastating cancer affects 750,000 people and has a five-year mortality rate of approximately 50 per cent if not detected and treated early.

The insidious nature of oral cancer means it is often detected at a later stage; up to half of people who are diagnosed with oral cancer have large tumours as oral cancer is often painless and unseen.

A further challenge is the limited tools to detect and monitor potential oral cancers and skin lesions over time; this forces clinicians to remove suspicious lesions by scalpel biopsy and assess pathology. A new research project aims to identify individuals who are likely to develop oral cancer, without invasive biopsies.

The Melbourne University Dental School has partnered with Victorian company OptiScan, to improve screening and early diagnosis of oral cancer.

The project is led by our team at the Melbourne Dental School and uses Optiscan’s state-of-the-art confocal laser endomicroscope (CLE). Known as InVivage ™, the hand-held microscope uses a laser light and confocal optics to painlessly perform “digital biopsies”.

THE TECHNOLOGY OF CANCER DETECTION
Oral cancer can have a devastating impact on a person’s life – removing a cancer from the mouth and tongue can impact on a person’s speech, their ability to swallow and eat, and ultimately, their self-esteem.

With the hand-held confocal laser endomicroscope (CLE), tissue can be viewed in 3D with 1,000-times magnification.

What we want to ascertain through our trial is how we can use OptiScan’s technology to microscopically see tumour cells in our clinic, helping us to assess the tissue and determine if a biopsy or surgery is required there and then.

Although 95 per cent of the lesions we see are not cancerous, without a biopsy, which can be painful and invasive, it’s very difficult to determine which lesions are cancerous or not. The earlier the diagnosis can be made, and the least tissue we can remove – the better for the patient.

Oral cancers are often preceded by changes in the appearance, such as the colour and thickness of the skin of the mouth. These changes are considered to have the potential to grow an oral cancer and affect as many as one in 20 people. However, only around three to five per cent of people with these changes will develop an oral cancer.

Once a biopsy sample is taken, it’s is assessed by a pathologist to see if there is any cancer present.

Sometimes there are changes in the way the skin is growing, called dysplasia, which tells us there may be an increased risk of cancer developing in the future. Still, this assessment is a limited predictor and can only be made on the small piece of skin that has been sampled.

OptiScan’s confocal laser endoscope allows microscopic visualisation of oral skin in real time.

MAPPING THE MOUTH
With the hand-held confocal laser endomicroscope (CLE), tissue can be viewed in 3D with 1,000-times magnification.

This could allow clinicians and surgeons to diagnose cancerous tissue in real time, reducing or eliminating the need to have one or more biopsies taken and sent to a laboratory for analysis.

Alongside trialing the CLE, our project also aims to develop software to comprehensively record an annotated map of the patient’s mouth with Optiscan as well as our other project partner, MoleMap. This means we could compare a patient’s mouth map the next time that they come in, to assess any changes. We can also use special dyes that show us all the cells in the skin surface or another that only binds to molecules that are found more commonly in cancer, identifying potential ‘hot spots’ of skin growth.

Our broader Mouthmap™ project will enable a detailed collection of a large amount data to compare this new CLE technology to diagnosis using standard light microscopy; this has the potential to establish a new standard of diagnosis and allow advancement of both human and computer algorithm-based learning.

THE NEXT STEPS
Our research aims to provide a solid foundation to advance towards clinical trials and recommendations to changes in standard of care.

The participants in this clinical study will be recruited by invitation from our main oral pre-cancer referral centre, networked with regional community centres where only individuals on healthcare card and pension card holders are eligible for treatment. This is important because lower socioeconomic status ,as well as older age, are both considered risk factors for oral cancer.

Our goal is that this technology will help to reduce the need for scalpel biopsy in the future, allowing for more comprehensive assessment of skin changes in the mouth and earlier detection of oral cancer.

The Melbourne Dental School trial is due to commence in September this year, by referral.

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NSAID use may improve overall survival during chemoradiation for patients with HNSCC

Source: www.cancernetwork.com
Author: Hannah Slater

This study demonstrated a possible advantage in overall survival for patients taking NSAIDs during chemoradiation for head and neck squamous cell carcinoma.

A study published in JAMA Network Open suggested a possible advantage in overall survival (OS) for patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) during chemoradiation for head and neck squamous cell carcinoma (HNSCC).

However, researchers suggested that future studies evaluating this association are warranted.

“This large, retrospective cohort study suggests a significant association with improved OS for patients with HNSCC taking NSAIDs during definitive CRT,” the authors wrote. “While the change in LC with NSAID use was not significant, future studies should continue to evaluate this possibility.”

Overall, 460 patients with HNSCC who were treated with chemoradiation therapy (CRT) at a single institution between January 1, 2005 and August 1, 2017 were included in the study, including 201 patients (43.7%) who were taking NSAIDs during treatment. Patient and tumor characteristics included age, race/ethnicity, smoking status, alcohol use, comorbidities (respiratory, cardiovascular, immune, renal, endocrine), disease stage, human papillomavirus (HPV) status, and treatment duration.

On univariate analysis, NSAID use (hazard ratio [HR], 0.63; 95% CI, 0.43-0.92; P = 0.02) was associated with better OS. Moreover, on Cox regression analysis, after backward selection adjustment for possibly confounding factors such as age, smoking status, primary tumor site, human papillomavirus status, diabetes, stroke, and hyperlipidemia, NSAID use continued to be significantly associated with better OS (HR, 0.59; 95% CI, 0.38-0.90; P = 0.02).

Even further, at 5 years NSAID use was associated with significantly better OS compared with those who did not take concurrent NSAIDs (63.6% [56 of 88 patients]; 95% CI, 58%-73% vs 56.1% [83 of 148 patients]; 95% CI, 50%-63%; P = 0.03).

However, NSAID use was not associated with better disease-specific survival (DSS) in univariate (HR, 0.82; 95% CI, 0.48-1.41; P = 0.47) or multivariate (HR, 0.98; 95% CI, 0.57-1.70; P = 0.44) analysis. NSAID use was also not associated with better response to treatment (HR, 1.44; 95% CI, 0.91-2.27; P = 0.12) or distant failure (HR, 1.12; 95% CI, 0.68-1.84; P = 0.65). Furthermore, change in local control with NSAID use was not found to be statistically significant (HR, 0.59; 95% CI, 0.31-1.10; P = 0.10).

“This suggests the observed survival advantage may be associated with the cardiovascular benefits of NSAIDs rather than any chemoprotective properties they may have, particularly because there was a higher proportion of patients with diabetes and coronary artery disease in the group taking NSAIDs,” the authors wrote. “This is increasingly important because the risk of noncancer death now surpasses that of cancer death, with heart disease being the leading cause of noncancer mortality.”

“The fact that anticoagulants were not associated with improved OS while NSAIDs were suggests that the cyclooxygenase mechanism may be a contributing factor to survival,” the authors continued. “This mechanism may be a combination of local recurrence reduction through cyclooxygenase inhibition and treatment of underlying cardiovascular disease.”

Prior research has suggested that PIK3CA variations may be a clinically useful marker to identify which patients with HNSCC will benefit from NSAID use; however, the investigators suggested that until such testing is routine, the current data indicates that giving daily aspirin to patients with HNSCC who are receiving CRT may be associated with improved survival.

Notably, though the researchers had access to patient comorbidity data, they did not have access to the reason why patients were prescribed regular NSAID use, nor were they aware of the duration of use. However, the majority of patients who were taking NSAIDs at the time of consultation noted that they were taking a “baby” (81-mg) aspirin, which was continued during CRT.

Reference:
Iovoli AJ, Hermann GM, Ma SJ, et al. Association of Nonsteroidal Anti-inflammatory Drug Use With Survival in Patients With Squamous Cell Carcinoma of the Head and Neck Treated With Chemoradiation Therapy. JAMA Network Open.

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