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‘On the rise:’ Immunotherapy options for head and neck cancer

Source: www.curetoday.com
Author: Kristie L. Kahl

On behalf of the Head and Neck Cancer Alliance, Dr. Michael Moore spoke with CURE® about emerging therapies that potentially offer exciting new options for the future.

Although rates of head and neck cancer have risen, in part because of the human papillomavirus (HPV), emerging therapies such as targeted agents and immunotherapies are paving the way for future treatment of the disease, according to Dr. Michael Moore.

“I would say (immunotherapy) is probably one of the more exciting parts of what we’ve learned about head and neck cancer in recent years,” he told CURE® as a part of its “Speaking Out” video series.

On behalf of the Head and Neck Cancer Alliance, CURE® spoke with Moore, associate professor of otolaryngology-head and neck surgery and chief of head and neck surgery at Indiana University School of Medicine in Indianapolis, about targeted therapies, immunotherapy and how clinical trials are leading the way for future treatments.

How have genomics and targeted therapies played a role in head and neck cancer treatment?

Well, I would say it’s an emerging role. And it’s not used as commonly in head-neck cancer as it is in some other areas. So molecular testing or targeted therapies essentially are looking at a very specific part of the tumor to see if we can develop a specific drug that will target just that; (the goal is to) weaken the cancer’s defense — that is one way to say it — and try to very specifically treat that cancer in a way that will give us the best chance of getting rid of it and potentially try to limit the side effects related to the treatments. This has become a little bit more common now that the ability to analyze these tumors has become more widely available across the country. But still, the majority of these types of treatment approaches will be in the context of a clinical trial.

Do we have any currently approved targeted therapies for head and neck cancer?

That’s a great question. I think these are kind of different and are emerging all the time. There are ones that are focused on very specific mutations, such as what’s called the BRAF mutation, which is one that can be present in melanoma or certain aggressive cancers, such as thyroid cancer. And other ones will target things like tyrosine kinase inhibitors that have a more focused route to try to combat these tumors. And then there are ones that will be discussed a little later, such as immuno-oncology drugs that focus on the program cell death ligand and the receptor to try to turn the body’s immune system back on. Another example is what’s called Erbitux (cetuximab), which is focusing on a specific receptor on cancer cells, really trying to exploit this particular difference in cancer cells compared with normal tissue to try to give the best chance of getting rid of the tumor, but minimizing the side effects of the treatment.
What role has immunotherapy had in head and neck cancer treatment?

Cancer has a way of almost turning off the local immune system. It blocks many of the local immune responses to it. Normally, the body would say, “Yeah, that’s not part of our normal tissue, we want to get rid of it.” And some cancers have a way of blocking that. These immunotherapies have a way of almost inhibiting that blockage, if you will, or turning the immune system back on and allowing your own body’s immune system to fight these tumors. These can be incredibly effective. The challenge is if they’re only effective in a small minority of cancers. And so, when they do work, they can work extremely well and can give really good and long-lasting results. But in a high percentage of patients, the responses are much more modest or (patients) may not even respond at all.

Can you discuss the currently available immunotherapies for head and neck cancer?

There are two. Opdivo (nivolumab) is one that can be used in patients who have not responded or progressed despite standard therapy, including recent treatment with chemotherapy, including cisplatin. And then Keytruda (pembrolizumab) is another similar amino therapy that can be used and has actually achieved approval for use in the primary setting. When cancer comes back in an area that can’t be treated with either definitive surgery or definitive radiation therapy, you can use that as a next avenue for treatment. These are the two (Food and Drug Administration)-approved drugs that are out there. They also have ongoing studies where they’re being combined with other standard-of- care, primary treatments for head and neck cancer. I think in the next five to 10 years, they’ll likely be integrated much more on the front end of cancer therapy, rather than just offering them to those who don’t have other treatment options.

How do clinical trials help to advance these therapies, and why should patients consider joining one?

These are really what allows us to make our cancer treatment better. We constantly are. It’s not just going out and experimenting on people but, rather, we’re comparing these treatments to see how we can improve on the current standard approach to therapy. If you were to look back 50 to 60 years ago, all we had were big, morbid surgeries that people were put through and possibly adding radiation therapy. And then we added cisplatin, which is a drug that can be effective in enhancing the effects of radiation therapy. Now, as we add these other treatments, such as immunotherapy and other targeted therapies, the only way we know if they have any advantage over what we have to offer, currently, is to compare them in a clinical trial.

And with these clinical trials, those who have designed them have been very thoughtful in trying to do so in a way that compares them and then looks to see: Does that give us a benefit in getting rid of the cancer or curing the cancer, or at a minimum, slowing it down or giving a longer life? And/or does it give better quality of life or reduce the level of side effects? That’s what many of these clinical trials are. Some are adding new agents to see if those work better than other ones. For example, in the HPV-related cancer, some of the clinical trials are saying these respond fairly well to treatment. Can we actually back off on the severity of treatment, give them just as good of a cancer cure but (with) fewer long-term side effects? I think they’re critical as the only way we’re going to figure out how best to manage these types of cancers.

Personalized 3D-printed shields protect healthy tissue during radiotherapy

Source: physicsworld.com
Author: Jigar Dubal

Personalized 3D-printed devices for radioprotection of anatomical sites at high risk of radiation toxicity: intra-oral device (A), oesophageal device (B) and rectal device (C) generated from patient CT images. The area for protection is highlighted in red. (Courtesy: CC BY 4.0/Adv. Sci. 10.1002/advs.202100510)

One of the primary goals of radiation therapy is to deliver a large radiation dose to cancer cells whilst minimizing normal tissue toxicity. However, most cancer patients undergoing such treatments are likely to experience some side effects caused by irradiation of healthy tissue. The extent of this damage is dependent on the treatment location, with the most common toxicities involving the oral cavity and gastrointestinal tract.

Materials with a high atomic number (Z), often known as radiation-attenuating materials, can be used to shield normal tissue from radiation. However, integrating such materials into current patient treatment protocols has proven difficult due to the inability to rapidly create personalized shielding devices.

James Byrne and colleagues at Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Massachusetts General Hospital and MIT have addressed this need. The team has developed 3D-printed radiation shields, based on patient CT scans, incorporating radiation-attenuating materials to reduce the toxicity to healthy tissue.

Producing personalized 3D-printed shielding
Before a patient undergoes radiotherapy, they undergo CT scans to provide anatomical information that is used to plan their treatment. Byrne and his colleagues utilize these CT images to design personalized radio-protective devices, which they produce through 3D printing.

To determine the most appropriate shielding materials for the device, the researchers tested various elements and alloys, including liquids, with a high Z number. They characterized these materials by measuring their relative mass attenuation coefficients. From this, the team determined that elemental materials demonstrated greater radiation shielding than alloys or composites, and that mercury largely outperformed all other liquids. They then incorporated the high-Z materials into the personalized 3D-printed devices. The devices were made such that the shielding material could be removed to reduce artefacts during CT imaging and replaced prior to treatment.

To evaluate the device’s ability to shield healthy tissue from radiation, the team treated 14 rats with single-dose irradiation, half with and half without radio-protective devices in place, and examined the incidence of toxicities such as oral mucositis and proctitis.

The group also simulated clinical radiation treatments by modelling the radio-protective devices in the treatment planning software. The dose distributions with and without shielding were compared to evaluate the dosimetric impact of the device. The researchers simulated treatments of prostate and head-and-neck cancer patients, selecting the appropriate positioning of the device based on the regions of increased radiation exposure.

Evaluation of radio-protective devices
Histopathological analysis revealed that only one of seven rats with radio-protective devices in place during treatment suffered ulceration on the surface of the tongue. In contrast, all seven control rats, with no device in place, experienced extensive ulcerations on the tongue surface.

The clinical simulations identified that using radio-protective devices during prostate cancer treatment could reduce the dose to healthy tissue by 15% without reducing the dose delivered to the tumour. For the head-and-neck cancer treatment, the dose absorbed by inner-cheek tissue was reduced by 30%.

The results clearly show that the radio-protective devices may improve patient comfort throughout the course of treatment. “Our results support the feasibility of personalized devices for reduction of radiation dose and associated side effects” claims Byrne.

Future clinical implementation
The benefits of using 3D-printed radio-protective devices in the clinic are clear. “This personalized approach could be applicable to a variety of cancers that respond to radiation therapy,” says Byrne.

The researchers acknowledge that full clinical translation of 3D-printed shielding devices will require further development. “Given the small sample size of our dosimetric studies, further investigation in larger cohorts is needed to validate these approaches,” they say.

The researchers publish their findings in Advanced Science.

Five reasons boys and young men need the HPV vaccine, too

Source: www.mskcc.org
Author: Memorial Sloan Kettering Cancer Center, News and Information

Rich Delgrosso found the lump while shaving. It was on the left side of his neck and it seemed to grow bigger by the day. He made an appointment with his ear, nose, and throat doctor.

“He said the odds were 50/50 that it was an infection,” recalls the 56-year-old father of two from Pleasantville, New York. “I asked, ‘What’s the other 50?’”

It was a possibility no one wanted to hear: Cancer. Rich underwent a biopsy and learned he had squamous cell carcinoma that had originated on the base of his tongue. His cancer, the doctor told him, was caused by the human papillomavirus (HPV).

Rich was shocked. “I knew HPV could cause cancer,” he says, “but I thought it was only cervical cancer in women.”

It’s true that HPV, a sexually transmitted virus, does cause the majority of cervical cancer cases in women. But it can also cause a variety of cancers in men, too, some of which are on the rise.

HPV led to a five-fold increase of head and neck cancers in young men from 2001 to 2017, according to data released at the 2021 American Society for Clinical Oncology annual meeting.

Memorial Sloan Kettering’s David Pfister, a medical oncologist who cares for people with head and neck cancer, says these cancer cases are just now emerging in people infected with the virus many years ago.

“Once the association between HPV infection and throat cancers was established, we better understood the significant increase in the rate of these cancers,” he says. “There is a delay between infection and the development of cancer, so there is a big reservoir of people already potentially at risk.”

But there is a way to prevent more than 90% of cancers caused by this virus: Get the HPV vaccine. It protects against head and neck cancers as well as anal cancer in both men and women. In men, it also protects against penile cancer, and in women, cervical cancer, vaginal cancer, and vulvar cancer. The vaccine is recommended for all children and can be given as early as age 9. It’s also approved for adults up to age 45.

Amidst growing concern about falling vaccination rates, MSK joined other National Cancer Institute-designated cancer centers in a May 2021 statement urging physicians, parents, and young adults to begin or keep up with HPV vaccinations, after they were interrupted by COVID-19. Early in the pandemic, HPV vaccination rates among adolescents fell by 75%. Since March 2020, an estimated one million doses of HPV vaccine have been missed by adolescents who have public insurance. That’s a decline of 21% from pre-pandemic levels.

Moreover, parents of boys are increasingly hesitant to have their sons vaccinated, according to a study in the journal Pediatrics.

MSK’s HPV Center is working to increase vaccination rates for everyone. Here are five reasons why it’s especially important for males.

1. Men get cancers caused by HPV in large numbers, too.
From 2013 to 2017, there were approximately 25,000 cases of HPV-associated cancers in women and 19,000 in men, according to the Centers for Disease Control and Prevention. More than four out of every ten cases of cancer caused by HPV are in men.

“HPV should be of concern to all since men and women are affected virtually the same by this virus,” says Abraham Aragones, an MSK physician who also studies public health.

2. There are now more cases of head and neck cancers than cervical cancers in America; HPV causes 70% of them, according to the CDC.
“My doctor told me that tumors of the neck and throat were getting more common in men,” Rich recalls.

Head and neck cancers are four times as common in men as they are in women.

3. There is no test for HPV cancers in males.
A Pap test detects early-stage cervical cancer in women. No such test exists for penile, anal, or head and neck cancers.

“Developing something like a Pap test for throat cancer would be a game-changer,” says Dr. Pfister. “When you compare the throat to the cervix, the anatomy of sites like the tonsils and the base of the tongue have hard-to-reach crevices the virus can hide in. Until an effective and reliable screening test is developed, patients should stay up to date on their HPV vaccines, know how the disease is acquired, and take any suspicious symptoms like a lump in the neck or blood in the phlegm to their doctor or dentist.”

4. The odds of getting HPV-related cancer increases with age.
“Today’s men are living longer than ever before, and that gives cancer more time to develop,” Dr. Aragones says. “Vaccination protects men from HPV-related cancers in the short and long term.”

5. The vaccine is just as safe for boys as it is girls.
The HPV vaccine went through years of rigorous safety testing before it was approved in 2006 to prevent cervical cancer in women and in 2009 to prevent HPV-related cancers in males. Since then, more than 100 million doses of the HPV vaccine have been given in the United States. Like any vaccine, there can be side effects, but they are minor, like arm soreness and fatigue. “The benefits of vaccinating against HPV far outweigh any potential risk of side effects,” says Dr. Aragones.

Rich made sure his teenage son got the HPV vaccine and says his younger daughter will follow suit.

“I didn’t want them to go through what I went through,” he says. After radiation and chemotherapy three years ago, Rich thankfully has shown no evidence of disease.

HPV-related cancers are usually able to be treated successfully. But preventing a cancer is far better than treating it, which makes the HPV vaccine a valuable weapon against cancer.

Study finds major anti-inflammatory immune activity that favors oral cancer tumors

Source: medicalxpress.com
Author: MELISA Institute

A collaborative research led by immunologist Estefania Nova-Lamperti from the Universidad de Concepción (Chile), with a branch of researchers from MELISA Institute and other international academic centers, made progress in the understanding of molecular mechanisms preventing an effective antitumor immune response in oral cancer; The latter due to the production of chemical mediators that induce an anti-inflammatory regulatory response that favors tumor development through the vitamin D signaling pathway. The study was published in Frontiers in Immunology on May 7, 2021.

Oral cancer, 90% of which corresponds to the squamous cell type, is a neoplasm with a high mortality and morbidity rate, mainly because the diagnosis is made in late stages when metastases already exist, and where treatment produces serious physical and functional sequel among survivors.

It is well known that the immune system plays a key role in the development of cancer, either by stimulating pathways that play an anti-tumor role or, conversely, by generating an anti-inflammatory environment that allows the tumor to grow and be spread.

The main biological agents of the immune system are lymphocytes or T cells, which have different functions or phenotypes. In cancer, the presence of regulatory T cells (Tregs) and helper T cells type 2 (Th2) are associated with a worse prognosis, whereas the responses of helper T cells type 1 (Th1) within tumors, in general, show a better prognosis.

Dr. Nova-Lamperti points out that a key question in oral cancer is how an anti-inflammatory microenvironment is induced, boosting tumors growth. To date, “the immunoregulatory mechanisms associated with this change in the immune response are unknown and it is not acknowledged whether they come from or are external to the tumor,” explains the immunologist.

Using flow cytometry techniques, the research team was able to feature the T-cell phenotypes predominant in biopsies of 15 patients with oral cancer and compared them with the T-cell populations found in biopsies of 16 disease-free controls. Thus, they identified a predominant distribution of T cells expressing CCR8+ receptors (generally abundant in skin tissues), Th2-like regulatory T cells, and a small population of Th1 cells.

Based on these new findings, the researchers hypothesized that the tumor microenvironment obtained from biopsy cultures of patients with oral cancer, which contains the factors secreted by tumor cells (known as secretome), had the ability to induce an anti-inflammatory phenotype itself. To test this assumption, Nova-Lamperti and her colleagues challenged immune T cells subpopulations with the cancer secretome and, using genomics and proteomics techniques, determined how the mRNA transcripts and proteins expressed by these cells are modified.

Notably, transcriptomics showed that oral cancer secretome induced the expression of a group of genes that control the vitamin D (VitD) signaling pathway in T cells. Moreover, the proteomics study, through high-resolution mass spectrometry, revealed the presence of several proteins associated with the production of prostaglandin E2 (PGE2) linked to VitD rapid signaling in cell membranes. In addition, the researchers found a reduction in the proteins that carry VitD into the cell.

Based on these findings, the researchers suggested that the decrease in the mobility of VitD promotes an increase in its concentration in the tumor microenvironment, inducing an anti-inflammatory phenotype favorable to the tumor. In new experiments, the researchers challenged T-cell cultures with VitD and PEG2, confirming that VitD induces a Th2 regulatory response with expression of CCR8, while the combination of VitD and PEG2 inhibited the production of small proteins called cytokines. The latter are important for the activation of the immune system. Additionally, the study showed that a cytokine that binds to the CCR8 receptor, known as chemokine CCL18, was overexpressed in tumors, favoring a vicious circle that stimulates the Tregs cells to ‘stagnate’ in the tumor microenvironment.

Regarding the effect of the study, the immunologist noted that “findings could be interesting for the development of biological therapies centered on antibodies capable of blocking the action of specific molecules that favor tumor growth. For example, in the case of oral cancer, a therapy that selectively blocks the CCR8 receptor or that normalizes the vitamin D signaling pathway could eventually slow tumor growth, decrease the sequel of surgical resections, and improve survival in these patients.” The researcher stressed the need to continue doing research in this regard.

Researcher Mauricio Hernández, a mass spectrometry expert at the MELISA Institute, stated that “collaborating in this research was challenging; the proteomics for this study required several time-consuming procedures to obtain optimal results. For example, because we dealt with cell culture media, each sample had to be depleted of abundant proteins such as albumin that ‘shield’ or make it difficult to detect smaller, less abundant proteins; then we performed an off-line fractionation to increase our identification capability. This encompasses a chromatography step to subdivide each sample, which substantially multiplies the number of runs on our mass spectrometer and increases the time in subsequent bioinformatic analysis.”

Finally, Prof. Elard Koch, senior researcher and Chairman at the MELISA Institute, said that they were pleased to be invited to participate in the study led by Dr. Nova-Lamperti; “Collaborating with our multi omics capabilities in research as relevant as this one is encouraging for our researchers and a key goal for our institute” Koch remarked.

More women being diagnosed with mouth cancer, researchers say

Source: www.9news.com.au
Author: Gabriella Rogers, Health Reporter

Head and neck surgeons say more women are being diagnosed with mouth cancer and research is underway to help unravel what’s fuelling the alarming trend.

“These mouth cancers historically occur in older men, particularly smokers and drinkers,” said Associate Professor Carsten Palme, Director of Head and Neck Surgery at Chris O’Brien Lifehouse.

But surgeons here and overseas have identified a rise in the number of women being diagnosed with cases increasing about 5 per cent each year.

Those women are not presenting with traditional risk factors and their diagnosis usually “comes out of the blue”.

“A lot of research at the moment at our institutions is being done to try and identify exactly what is happening and why,” Dr Palme said.

Dr Palme said his youngest patient had just finished her HSC.

“She was 18 she presented with an ulcer at the right side of her tongue which was initially thought to be a benign traumatic ulcer and she ended up having a stage three tongue cancer,” he said.

“We are commonly seeing women between the ages of 20 and 40 present to our clinics, pretty well on a weekly basis,” he said.

According to the Australian Institute of Health and Welfare, more than 5,000 Australians are diagnosed with head and neck cancers each year.

Doctors at Chris O’Brien Lifehouse are now routinely using innovative approaches to remove and rebuild a patient’s jaw to help cure their cancer.

Tara Flannery, aged 49, was diagnosed with squamous cell cancer in her gum and doctors said removing the entire top jaw would give her the best chance of a cure.

On its own, the surgery would cause significant cosmetic deformities and would make eating, swallowing and speaking extremely difficult.

Surgeons used skin grafts grown in the woman’s leg to form the upper gum. (9News)

The teacher feared she would have to stand up in front of 30 kids with a disfigured face.

“I didn’t want to stop teaching,” Ms Flannery said.

The Lifehouse team created a 3D model of Ms Flannery’s jaw which enabled them to virtually map out her complex operation.

“It means what we plan on the computer can then be executed at surgery. And for something as complicated as the jaw, it’s absolutely critical,” said Dr David Leinkram, Lifehouse Oral and Maxillofacial Surgeon.

The doctors used the position of Tara’s top and bottom teeth as a starting point for the reconstruction and worked backwards.

“So we want to keep those teeth exactly where they were before and then we plan the reconstruction and the immediate dental implant at that time,” Dr Palme said.

Six weeks before the major surgery, they placed titanium implants and skin grafts inside her calf bone called the fibula. The skin grafts would form her new upper gum. Three segments of that bone and nearby blood vessels would eventually be removed to build her new jaw.

During the pre-fabrication process in the leg, specialist dentists take a mould to help build a bridge for her new acrylic teeth.

“Tara is a phenomenal example of what we can achieve in this day and age,” said Dr Palme.

“Within the last few years we’ve been able to really automate this process, speed up this process and really make it part of our routine care delivery for these patients,” said Dr Palme.

Ms Flannery is now back in the classroom doing what she loves doing best, teaching. She doesn’t look like she has had her jaw removed and is ecstatic with the result.

“I get blown away when I think about it,” she said.

“Tara’s a rock star. You would hardly know she’s had such incredibly destructive surgery,” said Dr Palme.

Increased epigenetic age acceleration observed among patients with head and neck cancer

Source: www.healio.com
Author: Ryan Lawrence

Patients with head and neck cancer experienced an increase in epigenetic age acceleration, especially directly after treatment, which appeared associated with greater fatigue and inflammation, according to a study in Cancer.

“Our findings add to the body of evidence suggesting that long-term toxicity and possibly increased mortality incurred from anticancer treatments for patients with head and neck cancer may be related to increased epigenetic age acceleration and its association with inflammation,” Canhua Xiao, PhD, RN, FAAN, acting associate professor at Nell Hodgson Woodruff School of Nursing at Emory University, said in a press release.

Because fatigue is prominent among patients with head and neck cancer and has been linked to poorer quality of life and survival, as well as symptoms that significantly impact diet and physical activity, Xiao and colleagues hypothesized that cancer-related and treatment-related adverse events or morbidities may represent accelerated aging trajectories.

Their prospective, longitudinal analysis included 133 patients (mean age, 59.19 ± 10.16 years; 72% men; 82% white) with squamous cell carcinoma of the head and neck, no distant metastasis and no uncontrolled major organ disease. Most of the patients (54%) had been diagnosed with oropharyngeal cancer, and 90% of those cancers were HPV related. The majority of patients (80%) underwent concurrent chemoradiotherapy, and 71% of those who underwent chemotherapy received cisplatin.

Researchers assessed all patients at baseline (approximately 1 week before radiotherapy), immediately after completing radiotherapy, and at 6 months and 12 months after radiotherapy. They collected demographic and clinical variables through questionnaires or chart reviews, measuring fatigue at all four time points with the use of the Multidimensional Fatigue Inventory-20 and measuring inflammatory markers with standard techniques.

Additionally, Xiao and colleagues assessed blood DNA methylation with a proprietary bead chip (Infinium MethylationEPIC BeadChip Kit, Illumina) and calculated epigenetic age acceleration (EAA) with the Levine epigenetic clock (DNAmPhenoAge), adjusted for chronological age.

Results showed significant EAA changes over time, with the greatest increase of 4.9 years (P < .001) occurring at the end of radiotherapy and a nonsignificant increase of 0.3 years persisting at 1 year after treatment compared with baseline.

Post hoc analyses showed patients who received chemotherapy had a significant increase in EAA (4.7 years) at treatment completion vs. those who did not receive chemotherapy (P = .001), with a trend toward higher EAA (2.54 years) at 1 year after treatment among patients who received cisplatin vs. carboplatin/paclitaxel.

Researchers also observed associations of increased EAA with higher fatigue over time (P = .003). Post hoc analyses showed patients with severe fatigue, experienced by half of the study population at some point during the period, had higher EAA (3.1 years) over the course of the study than those with low fatigue (P < .001). The increase in EAA appeared even more prominent among patients with HPV-unrelated tumors and severe fatigue (5.63 years) vs. low fatigue (P < .018).

Inflammatory markers also appeared associated with significant increases in EAA over time, including high vs. low levels of C-reactive protein (by 4.6 years) and interleukin-6 (by 5.9 years; P < .001 for both). Each of these markers mediated the association between EAA and fatigue (C-reactive protein: B = 0.159; 95% CI, 0.06-0.279; interleukin-6: B = 0.106; 95% CI, 0.024-0.22).

Study limitations included a lack of standardization of blood-draw timing and the inclusion of mainly white men. Researchers called for further studies investigating the long-term relationship between EAA and later toxicities.

“Future studies could examine the vulnerabilities that may account for sustained high EAA, fatigue and inflammation among patients,” Xiao said in a press release.

Cancer-related fatigue is “an underrecognized problem” and is crucial in influencing patients’ treatment outcomes in addition to their quality of life, Kord M. Kober, PhD, assistant professor of physiological nursing at Helen Diller Family Comprehensive Cancer Center, and Sue S. Yom, MD, PhD, MAS, professor and vice chair in the strategic advisory department of radiation oncology and professor or otolaryngology-head and neck surgery, both at University of California, San Francisco, wrote in a corresponding editorial.

“Developing useable, efficient, systematized assessments of cancer-related fatigue should be prioritized because this would lead to increased clinical familiarity and a stronger foundation for developing and implementing effective treatment algorithms for patients at high risk,” Kober and Yom wrote. “Furthermore, the weight of the evidence seems to indicate that cancer-related fatigue is not just an ancillary symptom but a meaningful physiologic phenomenon reflecting a dangerous biology at work in these patients.”

References:
Xiao C, et al. Cancer. 2021;doi:10.1002/cncr.33641.
Kober KM and Yom SS. Cancer. 2021;doi:10.1002/cncr.33640.

NIH supports a new strategy to reduce side effects of head and neck cancer treatment

Source: www.news-medical.net
Author: Rice University, reviewed by Emily Henderson, B.Sc

A new strategy to reduce the side effects suffered by patients undergoing treatment for head and neck cancers now has the support of the National Institutes of Health.

Andrew Schaefer, the Noah Harding Chair and a professor of computational and applied mathematics and computer science at Rice’s Brown School of Engineering, won a prestigious four-year R01 grant for $1.2 million to develop a personalized approach to adaptive radiation therapy (ART) for head and neck cancers.

The goal of the study is a tool to personalize chemo- and radiation-based therapies that both reduce risks to patients and make the process more efficient for providers.

Schaefer is working with co-investigators Clifton Fuller, an associate professor in the Department of Radiation Oncology at the University of Texas MD Anderson Cancer Center, and Rice colleagues Mallesh Pai, an associate professor of economics, and Joey Huchette, an assistant professor of computational and applied mathematics.

Head and neck cancers account for nearly 3% of cancers in the United States and most commonly affect people over 50, mostly men. Of primary concern is unwanted damage from radiation to structures adjacent to tumors, including glands, bone and muscle related to speech, eating and swallowing.

The grant, which is administered by the National Cancer Institute, will allow Schaefer and his team to develop a mathematical model that helps providers optimize both individual treatment strategies for patients and health care providers’ policies for the implementation of new technology.

ART will take advantage of computerized tomography (CT) technology in use since the early 2000s. It allows clinicians who gather real-time images of changes in a tumor to adapt treatment. ART-based strategies vary. The simplest “fixed-interval” approach requires a midstream reconsideration of therapy, and the most sophisticated “cascade” approach involves daily evaluation of tumors and continual adjustment of chemotherapy and/or radiation in response to changes in tumor geometry.

Schaefer and colleagues plan to feed imaging data into custom Markov decision processes, mathematical models commonly used to optimize decisions over time in dynamic situations. Schaefer compared the models to maps that suggest how a driver should change course when an unexpected roadblock appears.

“The models are going to allow us to adaptively decide how we’re going to adjust a treatment,” he said. “It will be real-time navigation, not through a physical space but through all the treatment options.”

ART, he said, replaces one-time, up-front decisions about a patient’s treatment with a set of points requiring a decision to replan, thus balancing the needs of all parties.

Schaefer, who earned bachelor’s and master’s degrees in computational and applied mathematics at Rice in 1994, said MD Anderson has one of the first MRI-guided linear accelerators (MR-linAc), which will enable cascade treatment plans by allowing for real-time views of tumors during therapy.

He said the team will develop the best cascade treatment plans for a variety of patients under conditions of uncertainty, and come up with the best simple policies for implementing those policies at cancer centers without MR-linAc machines. The researchers will also work to understand the insurance implications in all treatment plans.

“Just like with other drug regimes, some bodies are going to tolerate radiation very well and some not at all,” Schaefer said. “With head and neck cancers, there are a lot of organs we’re trying to protect because we can’t deliver radiation to precisely the tumor and nothing else around it.

“So there are trade-offs,” he said. “This program will let us adapt our plan of treatment to what we see in terms of toxicity to the patient and what happens to the tumor. This new generation of machines is going to allow us to re-plan treatment in a much more agile fashion.”

For facilities without the latest imaging technology, “We’re going to be able to say, these are the adjustments we make for patients in a similar situation,” Schaefer said.

Naveris’ new saliva test detects head and neck cancer

Source: www.biospace.com/
Author: staff

A new clinically-validated saliva test has been shown to detect HPV-associated head and neck cancer with high accuracy, a first-of-its-kind study result.

Researchers at Washington University School of Medicine in St. Louis used the Naveris, Inc. test to analyze saliva for sequences of the human papilloma virus (HPV) genome that are specific for HPV DNA released from malignant tumors. The test successfully distinguishes this tumor-tissue modified virus from non-cancerous sources of HPV DNA and precisely measures the number of tumor-tissue modified viral HPV (TTMV-HPV) DNA strands present in a saliva sample.

The study results point to the potential for a significant improvement in early detection of the most common type of head and neck cancer, HPV-associated oropharyngeal squamous cell carcinoma.

“Naveris’ patient-friendly saliva test has the potential to radically advance early detection of HPV-positive head and neck cancer, which has been growing rapidly among men in the United States. Early detection of these cancers would make a dramatic difference in patient outcomes,” said Piyush Gupta, PhD, CEO of Naveris.

The study quantified participants’ tumor-tissue modified viral HPV DNA in saliva samples and compared it to the levels found in their blood by utilizing Naveris’ NavDx® test. The results showed that TTMV-HPV DNA was commonly found in the saliva of HPV-associated head and neck cancer patients (44/46 cases), and at 18 times higher levels in the saliva samples than in the blood samples. One sample had undetectable TTMV-HPV and one was indeterminate for HPV DNA.

Washington University researchers are presenting an abstract of the study at the American Society of Clinical Oncology (ASCO) 2021 annual meeting.

“The results of our study highlight the potential of accurately analyzing saliva to improve the early detection of HPV-associated oropharyngeal squamous cell carcinoma. If validated in larger studies, this test could lead to earlier diagnosis and treatment,” said the study’s principal investigator Jose P. Zevallos, MD, chief of the division of Head and Neck Surgery in the Department of Otolaryngology at Washington University School of Medicine.

Naveris’ new saliva test is based upon the proprietary technology employed by the NavDx® blood test that is in use at centers of excellence treating HPV-associated oropharyngeal cancer across the United States. NavDx® is a liquid biopsy test that detects HPV-associated head and neck cancer earlier than is possible with imaging and is provided exclusively in the United States through the Naveris national reference CAP-accredited laboratory.

About Oropharyngeal Cancer:
Oropharyngeal cancer, which can develop at the base of the tongue, tonsils, and the middle part of the throat, used to be closely associated with smoking and heavy drinking. Today, however, oropharyngeal cancer is primarily caused by human papillomavirus (HPV) infection, the most common sexually transmitted virus and infection in the United States. More than one of five U.S. adults are infected with a high-risk strain of HPV that can potentially develop into cancer.1

Cases of HPV-positive oropharyngeal cancer have been increasing at an exponential rate among men in the United States over the last two decades2. About 54,000 cases of oropharyngeal and oral cavity cancer are expected in the nation this year and more than 10,000 deaths.3

Oropharyngeal cancers usually are not identified early because they grow slowly in locations that are not easy to see. By the time the cancers are recognized they frequently have spread to the lymph nodes and are difficult to treat. Early detection, however, enables highly effective treatment.

About Naveris, Inc.
Naveris, Inc. is a molecular diagnostics company developing and commercializing novel blood and saliva tests to enhance the early detection and clinical management of viral-associated cancers. The company’s NavDx® blood test, which uses proprietary technology to detect tumor tissue modified HPV, is in use at leading cancer treatment centers and academic medical centers throughout the United States.

Bacteria and fungi might increase risk of head and neck cancers

Source: www.medicalnewstoday.com
Author: staff

Head and neck squamous cell carcinoma (HNSCC), which develops in the mucous membranes of the mouth, nose, and throat, is the sixth most common type of cancer worldwide. Globally, there were approximately 890,000 new cases of HNSCC and 450,000 associated deaths in 2018.

Risk factorsTrusted Source for HNSCC include tobacco use, alcohol consumption, and human papillomavirus (HPV) infection.

Researchers at São Paulo State University (UNESP) in Araraquara, Brazil, hope that learning more about metabolomicsTrusted Source — the analysis of metabolites in an organism — will prove key to developing a better understanding of these types of cancer.

The researchers conducted a laboratory study that showed how fungi and bacteria can activate genes associated with head and neck tumors. The study appears in Frontiers in Cellular and Infection Microbiology.

The researchers’ work suggests that the metabolism of biofilms stimulates tumor cells by favoring cell signaling pathways that are required for tumor development. Biofilms occur when bacteria congregate and form a community.

Specifically, the study details how biofilms secrete metabolites, which are the intermediate or end product of metabolism. These metabolites can modify the expression of genes that experts associate with tumor cell growth.

“It was very exciting for us that we found a relationship between the metabolites of these microbes [and cell behavior],” Dr. Paula Aboud Barbugli, a professor at UNESP’s Araraquara Dental School and co-leader of the study, told Medical News Today.

Microorganisms and cancer cells
The researchers introduced metabolites from biofilms to healthy oral epithelial cells and HNSCC cells. Specifically, they used metabolites produced by Candida albicans (C. albicans), a highly prevalent fungus in humans, and Staphylococcus aureus (S. aureus), the bacteria that cause staph infections.

The scientists stimulated both healthy and neoplastic cells for either 4 or 24 hours with single and dual biofilms of C. albicans and S. aureus.

They found that the biofilms promoted changes in cell gene expression in both normal and neoplastic oral epithelial cell lines. “They are exerting some effect on cellular behavior,” Dr. Barbugli explained to MNT.

Another key finding of the study is that molecules secreted by these microorganisms in biofilms may modify host cell activities far away from the primary infection site. “Our patients who wear [dentures], they have lots of C. albicans,” Dr. Barbugli said. “It may influence some cancers of the esophagus or [cancer in some other location of the body].”

Oral hygiene
The microorganisms used by the researchers were not selected at random. Authors of a 2005 study foundC. albicans isolated in 66.7% of studied dentures, and S. aureus — in 49.5%.

A 2017 study, which was led by many of the same UNESP researchers, found that soluble factors in methicillin-sensitive C. albicans and S. aureus biofilms promoted cell death and inflammatory responses.

“Control of biofilms, including denture and oral cavity hygiene, is extremely important to minimize inflammatory processes, as shown by our prior research and the study just published, which points to interference with the expression of genes associated with tumor progression,” said Dr. Carlos Eduardo Vergani, a professor at UNESP’s Araraquara Dental School and principal investigator of the research.

Dr. Barbugli told MNT that she would like to see more dentists and doctors work together to study the oral microbiome, which consists of more than 700 speciesTrusted Source of bacteria. “We need lots of research in this area,” she said.

Next steps
Next, the UNESP researchers plan to study the prevalence of C. albicans and S. aureus biofilms in the dentures and oral cavities of people with HNSCC in Brazil to get an idea about whether those biofilms influence a person’s prognosis.

Dr. Barbugli is particularly interested in studying patients with HPV-negative HNSCC, which generally has a worse prognosisTrusted Source. “I think that the microbiome is highly influencing the behavior of the cells,” Dr. Barbugli told MNT.

Study finds major anti-inflammatory immune activity that favors oral cancer tumors

Source: medicalxpress.com
Author: Melisa Institute

A collaborative research led by immunologist Estefania Nova-Lamperti from the Universidad de Concepción (Chile), with a branch of researchers from MELISA Institute and other international academic centers, made progress in the understanding of molecular mechanisms preventing an effective antitumor immune response in oral cancer; The latter due to the production of chemical mediators that induce an anti-inflammatory regulatory response that favors tumor development through the vitamin D signaling pathway. The study was published in Frontiers in Immunology on May 7, 2021.

Oral cancer, 90% of which corresponds to the squamous cell type, is a neoplasm with a high mortality and morbidity rate, mainly because the diagnosis is made in late stages when metastases already exist, and where treatment produces serious physical and functional sequel among survivors.

It is well known that the immune system plays a key role in the development of cancer, either by stimulating pathways that play an anti-tumor role or, conversely, by generating an anti-inflammatory environment that allows the tumor to grow and be spread.

The main biological agents of the immune system are lymphocytes or T cells, which have different functions or phenotypes. In cancer, the presence of regulatory T cells (Tregs) and helper T cells type 2 (Th2) are associated with a worse prognosis, whereas the responses of helper T cells type 1 (Th1) within tumors, in general, show a better prognosis.

Dr. Nova-Lamperti points out that a key question in oral cancer is how an anti-inflammatory microenvironment is induced, boosting tumors growth. To date, “the immunoregulatory mechanisms associated with this change in the immune response are unknown and it is not acknowledged whether they come from or are external to the tumor,” explains the immunologist.

Using flow cytometry techniques, the research team was able to feature the T-cell phenotypes predominant in biopsies of 15 patients with oral cancer and compared them with the T-cell populations found in biopsies of 16 disease-free controls. Thus, they identified a predominant distribution of T cells expressing CCR8+ receptors (generally abundant in skin tissues), Th2-like regulatory T cells, and a small population of Th1 cells.

Based on these new findings, the researchers hypothesized that the tumor microenvironment obtained from biopsy cultures of patients with oral cancer, which contains the factors secreted by tumor cells (known as secretome), had the ability to induce an anti-inflammatory phenotype itself. To test this assumption, Nova-Lamperti and her colleagues challenged immune T cells subpopulations with the cancer secretome and, using genomics and proteomics techniques, determined how the mRNA transcripts and proteins expressed by these cells are modified.

Notably, transcriptomics showed that oral cancer secretome induced the expression of a group of genes that control the vitamin D (VitD) signaling pathway in T cells. Moreover, the proteomics study, through high-resolution mass spectrometry, revealed the presence of several proteins associated with the production of prostaglandin E2 (PGE2) linked to VitD rapid signaling in cell membranes. In addition, the researchers found a reduction in the proteins that carry VitD into the cell.

Based on these findings, the researchers suggested that the decrease in the mobility of VitD promotes an increase in its concentration in the tumor microenvironment, inducing an anti-inflammatory phenotype favorable to the tumor. In new experiments, the researchers challenged T-cell cultures with VitD and PEG2, confirming that VitD induces a Th2 regulatory response with expression of CCR8, while the combination of VitD and PEG2 inhibited the production of small proteins called cytokines. The latter are important for the activation of the immune system. Additionally, the study showed that a cytokine that binds to the CCR8 receptor, known as chemokine CCL18, was overexpressed in tumors, favoring a vicious circle that stimulates the Tregs cells to ‘stagnate’ in the tumor microenvironment.

Regarding the effect of the study, the immunologist noted that “findings could be interesting for the development of biological therapies centered on antibodies capable of blocking the action of specific molecules that favor tumor growth. For example, in the case of oral cancer, a therapy that selectively blocks the CCR8 receptor or that normalizes the vitamin D signaling pathway could eventually slow tumor growth, decrease the sequel of surgical resections, and improve survival in these patients.” The researcher stressed the need to continue doing research in this regard.

Researcher Mauricio Hernández, a mass spectrometry expert at the MELISA Institute, stated that “collaborating in this research was challenging; the proteomics for this study required several time-consuming procedures to obtain optimal results. For example, because we dealt with cell culture media, each sample had to be depleted of abundant proteins such as albumin that ‘shield’ or make it difficult to detect smaller, less abundant proteins; then we performed an off-line fractionation to increase our identification capability. This encompasses a chromatography step to subdivide each sample, which substantially multiplies the number of runs on our mass spectrometer and increases the time in subsequent bioinformatic analysis.”

Finally, Prof. Elard Koch, senior researcher and Chairman at the MELISA Institute, said that they were pleased to be invited to participate in the study led by Dr. Nova-Lamperti; “Collaborating with our multi omics capabilities in research as relevant as this one is encouraging for our researchers and a key goal for our institute” Koch remarked.

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