Minimally-invasive treatment option for early stage oral cancer reduces recovery time, improves survival

Source: www.newswise.com
Author: Henry Ford Health System

Henry Ford Cancer Institute is a leader in providing a minimally invasive procedure called a sentinel lymph node biopsy for patients with early stage oral cancer. The biopsy can be performed at the same time oral cancer is surgically removed, and it can determine if the cancer has spread to nearby lymph nodes.

For Henry Ford patient Marlene Calverley, the biopsy meant having three lymph nodes removed versus 30-60 lymph nodes, and a two-inch scar instead of a five-to-six-inch scar. It also meant no neck drains, no physical therapy, and a decreased risk of complications.

“We are one of the few – if not the first – medical center in the State of Michigan to adopt this new paradigm for treating early oral cavity squamous cell cancers,” says head and neck cancer surgeon Tamer A. Ghanem M.D., Ph.D., director of Growth, Access, and Service for the Department of Otolaryngology at Henry Ford Cancer Institute. This new paradigm is based on a standard treatment for breast cancer and melanoma skin cancer.

The early data shows that sentinel lymph node biopsy may improve patients’ survival rate. Research also demonstrates a significant decrease in recovery time, complications, and effects attributed to a treatment, says Steven Chang, M.D., director of the Head and Neck Oncology program and the Microvascular Surgery Division at the Henry Ford Cancer Institute.

Head and neck cancers are among the most common cancers in the U.S. and globally. At the time patients are first diagnosed with oral cancer, about 15-25 percent of them have hidden microscopic cancer cells in the lymph nodes of the neck.

During a routine dental exam, Calverley was told to watch a small spot on her tongue. Three years later, an oral surgeon discovered cancer. Knowing there was a significant chance of cancer spreading, the surgeon recommended a neck dissection to remove all the lymph nodes.

At Henry Ford, Dr. Chang would offer a new and more precise treatment approach.

Traditionally, when oral cancer is found, neck surgery is performed and all the lymph nodes are removed, whether they are known to be diseased or not. However, about 75-85 percent of the patients do not need this surgery. After surgery, patients may require neck drains, and some will experience shoulder and lip weakness caused by exposing and manipulating the nerves, says Dr. Chang. Also, patients will have a large scar and longer recovery time.

In the past, patients who had early oral cavity lesions and who were at risk for hidden cancer in the lymph nodes were routinely offered extensive neck surgery to find any diseased nodes. Now, we are offering a simple sentinel node biopsy to select patients to find diseased nodes, says Dr. Ghanem.

Calverley was one of those select patients. To eliminate the cancer, one-quarter of her tongue would need to be removed. When doctors at another medical center initially recommended having all of levels 1-4 removed – which could consist of 30-60 nodes in her neck – and grafting donor tissue onto her tongue, she sought a second and third opinion.

“Dr. Chang was the only one who offered to do the sentinel node biopsy and to have my tongue heal on its own,” says Calverley, a 72-year-old Rochester resident.

When Dr. Chang explained that the sentinel node biopsy is also done for women having a mastectomy, it was an easy decision for me, she said.

“I went home and prayed and spent two days talking to people about my decision,” she says. “Friends in the medical field agreed with me and asked, ‘Why would you have all the lymph nodes in your neck removed if they aren’t cancerous, and then deal with all the repercussions? It’s not necessary.’”

“I had my surgery in November, and my tongue is healing beautifully,” says Calverley.

“Only three nodes were removed, and my scar is only about two inches. It’s right in line with a wrinkle on my neck, and you can barely see it,” she says.

“Within three days, I was up and making pumpkin rolls for Thanksgiving,” says Calverley. She spent only one night in the hospital after the surgery.

The benefits of the biopsy are important. Compared to surgery that removes all the lymph nodes, sentinel lymph node biopsy lowers the risk of lymphedema, which causes a buildup of fluid and swelling in the body. Additionally, the biopsy involves mapping lymph nodes in the lower neck and opposite side of the neck – areas not typically included in the traditional approach. For cancer in the middle area of the head or neck, patients can avoid surgery on both sides of the neck.

The sentinel node biopsy procedure involves injecting into the oral cancer site a weak radioactive substance that marks white blood cells. The substance acts as a tracer and is picked up by the lymph vessels, travelling along the path most likely used by any cancer cells that might drain from the tumor to the lymph nodes. Depending on the patient, cancer cells may travel in different paths or patterns. The first lymph node that the substance goes to is called the sentinel lymph node. Imaging will find it and any other nodes containing the tracer.

The surgeon will remove the suspected lymph nodes along with the oral cancer, and a pathologist will immediately examine the tissue to determine if cancer is actually present in the nodes. If it is, the surgeon will perform a neck dissection to remove the diseased lymph nodes.

However, if the nodes are negative for cancer, then we will avoid a full neck surgery for the patient, says Dr. Ghanem. By using minimally-invasive procedures and personalized medicine, doctors at Henry Ford continue to advance their mission of improving patient outcomes.

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February, 2019|Oral Cancer News|

Merck’s Keytruda looks to zoom past Opdivo with fast head and neck cancer review

Source: Fierce Pharma
Date: February 11, 2019
Author: Carly Helfand

Merck & Co.’s Keytruda is duking it out with Bristol-Myers Squibb’s Opdivo in the head and neck cancer marketplace, but Keytruda just took one step toward a green light that would give it a big edge.

The FDA has tagged Merck’s approval application for the immuno-oncology superstar—alone or in tandem with chemo—with its priority review designation in previously untreated patients with head and neck cancer. The move, which Merck announced Monday, sets Keytruda up for a quick trip down the regulatory pathway; the agency expects to have a decision by June 10, Merck said.

FDA staffers based their decision on data Merck trotted out at last year’s European Society for Medical Oncology (ESMO) meeting in October. Results showed that solo Keytruda, when pitted against a standard-of-care regimen dubbed by doctors as “Extreme,” could cut the risk of death by 22% in patients testing positive for the biomarker PD-L1. In patients with high levels of PD-L1 in their tumors, that figure shot up to 39%.

And when paired with chemo, Keytruda pared down the risk of death by 23% regardless of patients’ PD-L1 status.

Based on “the limited interaction we’ve had with key opinion leaders, I think this is seen as practice-changing,” Roy Baynes, Merck SVP and head of global clinical development, said when the data were released. And in addition to shaping opinions on clinical practice, the results also confirmed Keytruda’s place in the second-line setting, where it had previously suffered a narrow trial miss.

If Merck can snag a go-ahead in new patients, it’ll be an option for the more than 65,000 patients diagnosed each year in the U.S., according to the company. It’ll also mean a major leg up on BMS, whose Opdivo only bears a second-line OK. And with untreated patients in line to get Keytruda, the number of patients eligible for Opdivo—because those who used Keytruda first wouldn’t be in line for a second round of PD-1 therapy—will presumably dwindle.

The two drugs have been battling it out in different tumor types since the early days of immuno-oncology, when both started off with FDA nods in melanoma. While Opdivo has held market leads in important areas including kidney cancer, it’s Keytruda that has the No. 1 position, thanks to its dominant status in lung cancer, the biggest arena for the medicines.

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February, 2019|Oral Cancer News|

Why salivary diagnostics for dental practices?

Source: www.dentistryiq.com
Author: Barbara Kreuger, MA, RDH

I recently had the opportunity to visit OralDNA Labs and learn more about the process of running salivary diagnostic tests. Admittedly, when I first heard about salivary diagnostics, I didn’t immediately embrace the tests and what they had to offer. I was not convinced that they were necessary, believing they would not change how we treat dental disease.

However, we’ve been fortunate to use salivary diagnostics in practice and see the benefits in our patients firsthand. These tests have proven to be a great addition to our prevention tool box. Salivary diagnostics can play an important role in helping us produce high quality outcomes for patients and create awareness of their oral-systemic risk factors.

Bacterial identification
There are numerous salivary diagnostic tests available. The most widely used test from OralDNA Labs is MyPerioPath, which tests for the 11 pathogens that are known to contribute to periodontal destruction.(1) Once the test reveals which pathogens are contributing to the patient’s periodontal disease, it also offers antibiotic recommendations that target these specific bacteria.

When combined with periodontal maintenance visits and patient homecare, this test can lower a patient’s bacterial load, thus increasing positive outcomes. Retesting has shown that this reduction in bacteria can have a dramatic effect. We’ve seen tough cases—patients who were compliant with homecare but still exhibited clinical signs of periodontal disease—that improved dramatically after being treated with the test’s recommended systemic antibiotic. Periodic monitoring with MyPerioPath combined with periodontal maintenance treatment can help keep patients’ oral health stable.

Genetic predisposition
In addition to bacterial profile testing, various tests from OralDNA labs can tell us a patient’s genetic predisposition toward inflammation. This can reveal one of the reasons why some patients continue to experience periodontal destruction after treatment despite compliance and lower quantities of periodontal pathogens. In addition, much of the research connecting oral health to systemic conditions reveals that it is a patient’s total inflammatory burden that puts someone at risk for a host of health problems.(2,3)

While the patient’s genetic profile cannot be changed, the knowledge that the person has an overactive inflammatory response can help the practitioner and patient understand that there is a need for more frequent continuing care, adjunctive therapies, or treatment with a periodontist. This information can also help patients manage and control their systemic health with the help of their physician.

Caries risk assessment
When we look beyond the patient’s periodontal health, salivary diagnostics can also test for the bacteria that are known to contribute to caries. When we have an objective measure of the quantity and types of cariogenic bacteria in the patient’s mouth, we can once again tailor treatments to reduce his or her caries risk and motivate the patient toward behavioral change. If we then combine the test with a caries risk assessment tool, we can use the test to monitor the effectiveness of these behavior changes. Knowing the patient’s risk allows us to encourage the person to use interventions, such as fluoride to re-mineralize teeth and xylitol to inhibit the bacterial metabolism.

Oral cancer screening
Finally, salivary diagnostics can also test for the presence of various human papillomavirus (HPV) strains that have been shown to cause oral cancer. According to the American Cancer Society, oral cancer will take the lives of 10,860 people this year, and HPV is now seen as the leading cause.(4,5) Early diagnosis is key and increases survival from a dismal 20% when discovered after it has metastasized to distant sites, to 93% when discovered early.(6)

Knowing a patient’s HPV status may prompt us to increase the frequency of someone’s oral cancer screenings, or to use adjunctive diagnostic tools such as oral anomaly detection devices to more closely monitor the patient and potentially catch the cancer at an earlier stage.

More and more research studies are correlating the various bacteria that cause periodontal disease to systemic conditions. The more we understand about a patient’s bacterial load and risk factors, the better equipped we can be to help manage periodontal disease and improve overall health. Salivary diagnostics can help us provide optimal care for patients, increasing our ability to provide them with positive outcomes through tailored treatment and patient education.

Barbara Kreuger, MA, RDH, earned a Bachelor of Science in dental hygiene from the University of Minnesota and holds a Master of Arts in organizational leadership from St. Mary’s University of Minnesota. She spent more than 18 years as a clinical dental hygienist before moving to her current role as dental hygiene senior specialist for Pacific Dental Services. Barbara is currently serving as president of the Minnesota Dental Hygienists’ Association.

References

1. Oral DNA tests. OralDNA website. https://www.oraldna.com/tests.html. Accessed February 1, 2019.
2. Hunter P. The inflammation theory of disease. The growing realization that chronic inflammation is crucial in many diseases opens new avenues for treatment. EMBO Rep. 2012;13(11):968-70.
3. Minihane AM, et al. Low-grade inflammation, diet composition and health: current research evidence and its translation. Brit Jour Nutrition. 2015;114(7):999–1012.
4. Key Statistics for Oral Cavity and Oropharyngeal Cancers. American Cancer Society website. https://www.cancer.org/cancer/oral-cavity-and-oropharyngeal-cancer/about/key-statistics.html. Accessed February 1, 2019.
5. HPV/Oral Cancer Facts. Oral Cancer Foundation website. https://oralcancerfoundation.org/understanding/hpv/hpv-oral-cancer-facts/. Accessed February 1, 2019.
6. Survival Rates for Oral Cavity and Oropharyngeal Cancer. American Cancer Society website. https://www.cancer.org/cancer/oral-cavity-and-oropharyngeal-cancer/detection-diagnosis-staging/survival-rates.html. Accessed February 1, 2019.

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February, 2019|Oral Cancer News|

‘They needed something more after treatment’

Source: www.nursingtimes.net
Author: Claire Reed

Lesley Taylor wanted to examine the lack of support for patients at the end of treatment, so the decision was made to explore the impact of a wellbeing clinic on care, Claire Read reports.

When the results of the study came back, they confirmed what Lesley Taylor and her colleagues had long suspected. The patients for whom they cared were getting good support for their actual medical issues, but their post-treatment needs weren’t always being identified or met.

Ms Taylor is the Macmillan advanced oncology nurse specialist at NHS Tayside, as well as the head and neck cancer nurse specialist at the same organisation. It was on these patients which Ms Taylor’s study was focused.

“We could look down into their mouths and throats and say there was no evidence of any cancer, and that was great, they appreciated that. But what we didn’t have time to do in that medically-led clinic was look at things like dry mouth, and swallow, and the emotional aspects and the social aspects that come alongside what are often life-changing diagnoses and treatments,” she remembers.

“It became clear they needed something very much more at the end of treatment.” And so the decision was taken to instigate a nurse and allied health professional-led wellbeing clinic. The idea was to provide the sort of support that had been lacking; the holistic look at someone’s life in the immediate aftermath of the end of treatment.

The team worked together to reshuffle how they saw patients, and found a rare spot in the hospital in which they could hold appointments: a dental suite. The impact was soon felt. “The new cohort of patients that were coming through seemed to be getting better quicker,” according to Ms Taylor.

At the same time, there was the know-ledge that the service could be refined further. A priority was finding a non-hospital setting in which to hold the clinics. “We were aware there was this in-built anxiety about coming back to the hospital each time you had to be checked – there were all these reminders of what they’d been through and how that made them feel.”

It was felt a move into the community would make most sense, not least because, this is the main setting for individuals’ lives post-treatment. “We needed to rehabilitate them away from hospital and back to what was their own life, although it might be very different from what it was before.”

That became possible when a space was secured at a purpose-built health centre on the edges of Dundee. The shift to the new facility brought with it a shift in patient group. The service was opened up to colorectal and prostate cancer patients as well as those with head and neck cancers. In the longer run, the aim is to open the service to anyone who has been through any form of cancer treatment.

It means, staff hope, there is no longer the sense of abandonment some patients had reported feeling at the end of active treatment. “For head and neck cancer patients, they would have six weeks of daily treatment and then no contact – at a time when they were probably at the height of their treatment toxicity. So we now see them at two weeks, and we can see them earlier than that if there’s a problem.”

It is a major service design change. But ask Ms Taylor how she and her colleagues achieved it, and she is matter of fact: “We just thought: ‘We’ve got to do this’.”

And so they simply rearranged their diaries and made the new clinic work, not going down the route of trying to secure additional funding and the associated bureaucracy.

Ms Taylor argues there are virtues to that sort of evidence-based ‘get on and do it’ approach, but she also urges nurses who want to drive service redesign to pay attention to the effect their innovations have.

“Gather your information as you go, so that when somebody turns around and says to you: ‘Well, do you think you’ve made a difference?’, you don’t have to hack back through all this information, which is there but may not have been collated properly. Keep a strict eye on the data you’re producing, so that you can say – ‘Look at the difference we have made’.”

In the case of the clinics, there is now clear evidence of just such a difference. “It seems to be in this cohort of patients who’ve gone through these wellbeing clinics that they’ve gone from having their feeding tubes in for on average six months to having their feeding tubes in for an average of three months – a 50% reduction,” she reports. “So I just think it’s made a huge difference to the patients.”

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February, 2019|Oral Cancer News|

Symptom combos suggesting laryngeal cancer identified

Source: www.physiciansweekly.com
Author: staff

New symptom combinations that may indicate early symptoms of laryngeal cancer have been identified, according to a study published online Jan. 28 in the British Journal of General Practice.

Elizabeth A. Shephard, Ph.D., from the University of Exeter Medical School in the United Kingdom, and colleagues conducted a matched case-control study of patients aged ≥40 years to examine the clinical features of laryngeal cancer with which patients presented to their general practitioner in the year before diagnosis.

The researchers identified 806 patients who were diagnosed with laryngeal cancer between 2000 and 2009; the patients were matched with 3,559 controls based on age, sex, and practice. Significant associations were identified for 10 features with laryngeal cancer: hoarseness (odds ratio, 904); sore throat, first attendance (odds ratio, 6.2); sore throat, reattendance (odds ratio, 7.7); dysphagia (odds ratio, 6.5); otalgia (odds ratio, 5); dyspnea, reattendance (odds ratio, 4.7); mouth symptoms (odds ratio, 4.7); recurrent chest infection (odds ratio, 4.5); insomnia (odds ratio, 2.7); and raised inflammatory markers (odds ratio, 2.5). The highest individual positive predictive value (PPV) was 2.7 percent for hoarseness. The symptom combinations of sore throat plus either dysphagia, dyspnea, or otalgia are not currently included in the National Institute for Health and Care Excellence (NICE) guidelines; PPVs for these combinations were >5 percent.

“These results expand current NICE guidance by identifying new symptom combinations that are associated with laryngeal cancer; they may help general practitioners to select more appropriate patients for referral,” the authors write.

Abstract/Full Text

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February, 2019|Oral Cancer News|

Dad-of-two, 35, dies after being told he was too young to have throat cancer

Source: www.mirror.co.uk
Author: Amber Hicks

Ryan Greenan went to his doctor in Edinburgh in September after he started having trouble swallowing, eating and drinking.

The 35-year-old from Scotland was advised his symptoms were most likely caused by reflux and anxiety, reports the Scotsman , despite his family having a history of throat cancer.

Ryan’s sister Kerry, 33, said her brother took this diagnosis at face value “because the general advice was that oesophageal cancer only really affected older people”.

However, the symptoms persisted and Ryan started to rapidly lose weight before collapsing at work in December. 

He was taken to hospital and it was then that a tumour was discovered in his throat and he was diagnosed with cancer on December 28.

There was more heartache when it was revealed it had also spread to his lungs and liver and there was nothing that could be done to save him.

Three weeks later Ryan sadly died.

His sister is now calling on doctors to thoroughly test for the illness, even in younger patients.

Kerry told the Scotsman : “When Ryan first went to the doctor, he was told it was anxiety and that he was too young for it to be cancer because he was only 35.

“He just took that as his diagnosis and didn’t go back because the general advice was that oesophageal cancer only really affected older people.

“If it had been picked up earlier, they could have operated, they could have given him chemotherapy, but after three months it had spread, there was nothing else they could do at that point.

“I’m just absolutely destroyed. I’m so angry. If they had caught it earlier, my big brother would still be here today.”

It was while Ryan, who has two daughters aged eight and 11, was receiving treatment that he proposed to partner Natasha Robertson, 35, on January 11.

Heartbroken Natasha told the Evening Telegraph : “Ryan was my soulmate. We were together for eight months and he just made me so happy during such a short time.”

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February, 2019|Oral Cancer News|

How aspirin may benefit some people with head and neck cancer

Source: www.medicalnewstoday.com
Author: Catharine Paddock PhD, fact checked by Paula Field

Recent research has tied regular use of nonsteroidal anti-inflammatory drugs, such as aspirin, to longer survival in some people with head and neck cancer.

The researchers propose that there should now be a clinical trial to test the effectiveness and safety of nonsteroidal anti-inflammatory drugs (NSAIDs) for this purpose. They suggest that the effect that they observed is likely due to the NSAIDs reducing prostaglandin E2, a molecule that promotes inflammation. A paper on their findings now features in the Journal of Experimental Medicine.

Head and neck cancers are cancers in which tumors develop in the nose, sinuses, larynx, throat, and mouth. In most cases, the tumors arise in the flat thin squamous cells that form the tissue lining of surfaces. For this reason, they bear the name head and neck squamous cell carcinomas (HNSCCs).

In the United States, people with HNSCCs account for around 4 percent of all those with cancer. These types of cancer also tend to have a lower rate of survival compared with many other types. The main risk factors for HNSCC are tobacco use, heavy use of alcohol, sun exposure, and infection with the human papillomavirus (HPV).

Aspirin and HNSCC
Previous research has suggested that taking aspirin regularly can reduce the risk of developing HNSCCs. However, the recent study is the first to link the use of aspirin and other NSAIDs to longer survival in some people who already have HNSCC.

It found that, among people with HNSCC and alterations in the PIK3CA gene, those who regularly used NSAIDs had a longer overall survival rate than those who did not. Regular use of NSAIDs appeared to make no difference to survival in people with HNSCC who did not have any PIK3CA gene alterations.

The researchers defined regular use of NSAIDs as using them at least twice a week for 6 months or longer.

“The present study,” says senior study author Prof. Jennifer R. Grandis M.D., who works in the Department of Otolaryngology at the University of California, San Francisco, “is the first to demonstrate that regular NSAID usage confers a significant clinical advantage in patients with PIK3CA-altered HNSCC.”

PIK3CA and cancer
The PIK3CA gene contains DNA code for the “catalytic subunit” of the signaling enzyme PI3K. The catalytic subunit is the trigger for the enzyme, which activates various signaling reactions in cells. Signals from PI3K are essential for cell survival and activities, such as growth, division, movement, material transport, and protein production. Around 35 percent of people with HNSCC have tumors that harbor “activating mutations” of PIK3CA note the authors.

Colorectal cancer studies have also revealed links between regular NSAID use and improved survival in people who have altered PIK3CA genes. However, they did not explain the underlying mechanism.

Prof. Grandis and colleagues examined medical records and tumor tissue samples belonging to 266 people with HNSCC. The tissue samples came from tumors that surgeons had removed. In most cases, the individuals then received treatment with chemotherapy, or radiotherapy, or both.

Overall survival rose from 45-78 percent
The investigators used the tissue samples to determine which people had altered PIK3CA genes. They then correlated these results against patterns of NSAID use from the medical records.

The analysis revealed that that overall survival increased from 45 to 78 percent in those who regularly took NSAIDs and whose tumors showed that they had an altered PIK3CA gene.

The researchers tested for two types of PIK3CA alterations: mutations and amplifications. They found that the type of alteration did not change the benefit to overall survival. Mutations are alterations in the “spelling” of DNA code, whereas amplification is when DNA sequences repeat. Amplification can lead to increased production of proteins.

The team then tested the effect of NSAIDs on a mouse model. They injected mice with cancer cells containing an altered PIK3CA gene. The mice that received NSAIDs grew much smaller tumors.

NSAIDs block prostaglandin E2 production
Further examination of the mice led the team to suggest that the NSAIDs reduced tumor growth by blocking prostaglandin E2 production.

Prostaglandin E2 has come up in studies of other cancers that have raised the possibility that a PI3K signaling pathway triggers this inflammation-promoting molecule.

The new findings suggest that the benefit of NSAIDs on survival might extend to other types of cancer where there is an altered PIK3CA gene. The discovery about NSAIDs blocking prostaglandin E2 in mice might explain the drugs’ mechanism of action in people with colorectal cancer and altered PIK3CA genes.

Prof, Grandis concludes that they could not make any “specific recommendations” about the use of NSAIDs because of lack of consistency in the dosage, timing, and type of NSAIDs covered by their study.

“But the magnitude of the apparent advantage, especially given the marked morbidity and mortality of this disease, warrants further study in a prospective, randomized clinical trial.”

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January, 2019|Oral Cancer News|

Tumor Mutational Burden Predicts Who Will Respond to Immunotherapy

The advent of immunotherapy has significantly shifted the treatment paradigm and prognosis for multiple advanced-stage cancers. In cancers like metastatic melanoma and non–small cell lung cancer (NSCLC), the treatment class has greatly improved survival rates.

However, not all patients respond to the treatments, highlighting the need for predictive biomarkers to determine which patients will benefit. Early reports and small cohorts have suggested high tumor mutational burden being associated with improved clinical response, and now a large study has confirmed the hypothesis.

“Given the potential toxicities of immunotherapy and the highly variable response to immune checkpoint inhibitors, as well as the significant economic cost of these agents, there is an urgent need for biomarkers that can predict immunotherapy response,” explained the researchers of the study.

Looking at data from more than 1000 patients with stage IV or metastatic disease for which immune checkpoint inhibitors are approved, including NSCLC, melanoma, renal cell carcinoma, bladder cancer, and head and neck cancer, researchers found that higher somatic tumor mutational burden is associated with improved overall survival.

Patients were treated with atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab, pembrolizumab, or tremelimumab. Tumor mutational burden was calculated by normalizing the number of somatic nonsynonymous mutations to the total number of megabases sequenced, and noting that mutational load varies across tumor types, the researchers defined tumor mutational burden within each cancer type.

The authors found that, across all cancers, more mutations translated into improved overall survival. The authors noted that the association remained even when removing NSCLC and melanoma from the analysis.

“Although the effect for some individual cancers did not reach statistical significance, possibly because of smaller sample size, the numerical trend of better overall survival was observed in nearly all cancer types, with glioma the clearest exception,” the authors wrote. These findings mirror real-world evidence, which has shown gliomas to be immunosuppressive and remain difficult to treat.

Of note, what constituted as high tumor mutational burden varied greatly by cancer type, which suggests that there is likely not a viable universal number that could define high tumor mutational burden and be predictive of response to immune checkpoint inhibitors across all cancers. While breast cancers and renal cell carcinomas only need 6 mutations per 1 million DNA to predictably respond well to immune checkpoint inhibitors, melanomas need 30.7 and colorectal cancers need 52.2.

According to the researchers, this can likely be explained by distinct tumor microenvironments as well as other factors that have shown to independently predict response, including clonality, immune infiltration, and immune cell exclusion.

Reference:

Samstein R, Lee C, Shoushtari A, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types [publihsed online January 14, 2019]. Nature. doi: 10.1038/s41588-018-0312-8.

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January, 2019|Oral Cancer News|

Researchers Uncover Major Clue In Predicting Response To Immunotherapy

Researchers at Memorial Sloan Kettering Cancer Center in New York have discovered that cancer cells with high numbers of faults in their DNA are more likely to respond to immune checkpoint inhibitors (ICI), a major class of immunotherapy drugs, which includes Keytruda.

The study, published today in Nature Genetics adds important pieces to the puzzle as to why some cancer patients respond to immunotherapy whereas others do not. The researchers measured ‘tumor mutation burden (TMB)’, essentially counting how many DNA faults a tumor contains by looking for errors in the DNA sequence.

“People assume that TMB is important in predicting response to immunotherapy in all cancers, but up until now, all we’ve had is data from small studies and clinical trials on mostly lung cancers and melanoma,” said Luc Morris, MD, surgical oncologist at Memorial Sloan Kettering Cancer Center and one of the lead authors of the paper.

The researchers studied the DNA of 1,662 patients with advanced cancer (classified as stage IV or metastatic disease) treated with one or more of several FDA-approved ICI drugs and DNA from 5,371 patients with advanced cancer who had not had ICI. They used a tool called MSK-IMPACT, which looks at just 3% of the coding-regions in DNA, but is correlated to the number of mutations in the genome.

“Is TMB associated with likelihood that immunotherapy has benefit? Is this true in all cancers? We wanted to find out whether TMB had broad applicability,” said Morris.

The researchers found that if they took the 20% of cancers in their data with the most mutations, these people responded better to ICI than those with lower numbers of mutations in their tumors.

However, this correlation did not hold true for all tumors, for example, in people with a type of brain cancer called glioma, those with TMB in the top 20% did no better on ICI than those with lower TMB. Also in breast cancer there was no conclusive evidence that a higher TMB predicted response to ICI, although the study included relatively few breast cancer patients as ICI is not currently widely used for the disease.

Researchers don’t exactly know why high numbers of mutations make cancers more susceptible to immunotherapy, but they do have a very plausible theory. They think that the more mutated a cell is, the more likely it is to produce incorrect, mangled proteins. These displayed on the cell surface are called neoantigens and they are so far from what would be considered normal, the immune system identifies them as foreign and attacks the cells.

This is not a unique study in concept, with previous research on a smaller number of cancers of specific types, notably lung and melanoma, indicating that TMB is likely predictive of immunotherapy response. However, it is the largest and most comprehensive study to date, providing the most persuasive evidence that this is true for a greater number of cancer types.

“Only in lung cancer is TMB being used in a clinical trial. Hopefully this data will give us permission to include it in future clinical trials on other cancer types,” said Morris.

However, some patients with high TMB don’t respond to ICI at all, so there is still work to be done to figure out why high TMB is not a universal predictor of response to ICI.

“TMB by itself is not going to give you a high confidence in predicting whether a patient is going to respond to immunotherapy or not. It is one biomarker for response, but a number of other factors are important. I would not suggest you take the data from this paper and apply it to a patient in the clinic,” said Morris.

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January, 2019|Oral Cancer News|

New app gives throat cancer patients their voice back

Source: www.straitstimes.com
Author: staff

Throat cancer patient Vlastimil Gular can say what he wants in his own voice thanks to technology that uses past recordings of his voice to create synthetic speech that can be played on his mobile phone via an app. Photo: AFP

Vlastimil Gular’s life took an unwelcome turn a year ago: minor surgery on his vocal cords revealed throat cancer, which led to the loss of his larynx and with it, his voice.

But the 51-year-old father of four is still chatting away using his own voice rather than the tinny timbre of a robot, thanks to an innovative app developed by two Czech universities.

“I find this very useful,” Mr Gular told AFP, using the app to type in what he wanted to say, in his own voice, via a mobile phone.

“I’m not very good at using the voice prosthesis,” he added, pointing at the hole the size of a large coin in his throat.

This small silicon device implanted in the throat allows people to speak by pressing the hole with their fingers to regulate airflow through the prosthesis and so create sound.

But Mr Gular prefers the new hi-tech voice app.

It was developed for patients set to lose their voice due to a laryngectomy, or removal of the larynx, a typical procedure for advanced stages of throat cancer.

The joint project of the University of West Bohemia in Pilsen, Prague’s Charles University and two private companies – CertiCon and SpeechTech – kicked off nearly two years ago.

The technology uses recordings of a patient’s voice to create synthetic speech that can be played on their mobile phones, tablets or laptops via the app.

Ideally, patients need to record more than 10,000 sentences to provide scientists with enough material to produce their synthetic voice.

“We edit together individual sounds of speech so we need a lot of sentences,” said Dr Jindrich Matousek, an expert on text-to-speech synthesis, speech modelling and acoustics who heads the project at the Pilsen university.

A Matter of Weeks
But there are drawbacks: Patients facing laryngectomies usually have little time or energy to do the recordings in the wake of a diagnosis that requires swift treatment.

“It’s usually a matter of weeks,” said Dr Barbora Repova, a doctor at the Motol University Hospital, working on the project for Charles University.

“The patients also have to tackle issues like their economic situation, their lives are turned upside down, and the last thing they want to do is to make the recording,” she told AFP.

To address these difficulties, scientists came up with a more streamlined method for the app, which is supported by the Technology Agency of the Czech Republic.

Working with fewer sentences – ideally 3,500 but as few as 300 – this method uses advanced statistical models such as artificial neural networks.

“You use speech models with certain parameters to generate synthesised speech,” said Dr Matousek.

“Having more data is still better, but you can achieve decent quality with less data of a given voice.”

The sentences are carefully selected and individual sounds have to be recorded several times, as they are pronounced differently next to different sounds or at the beginning and end of a word or sentence, he added.

So far, the Pilsen university has recorded 10 to 15 patients, according to Dr Matousek.

Besides Czech, the Pilsen scientists have also created synthesised speech samples in English, Russian and Slovak.

Baby Dinosaurs
Mr Gular – an upholsterer who lost his job due to his handicap – managed to record 477 sentences over the three weeks between his diagnosis and the operation.

But he was stressed and less than satisfied with the quality of his voice.

“Throat cancer patients often suffer from some form of dysphonia (hoarseness) before the surgery, so in combination with a limited speech sample, it makes the voice sound unnatural,” said Dr Repova.

In a studio at the Pilsen university meanwhile, entrepreneur Jana Huttova is recording outlandish phrases.

The 34-year-old mother of three faces the risk of losing her voice to minor throat surgery – an operation on her parathyroid gland.

“The Chechens have always preferred a dagger-like Kalashnikov,” she says, reading from the text before her.

“I have small kids and I want them to hear my own voice, not a robot,” Ms Huttova said.

Then she moved on to her next sentence: “We were attacked by a tyrannosaur’s baby dinosaurs.”

Connected to the Brain
Dr Matousek believes that in the future, patients will be able to use the app to record their voice at home using a specialised website to guide them through the process.

And he hopes that one day it will go even further.

“The ultimate vision is a miniature device connected to the brain, to the nerves linked to speech – then patients could control the device with their thoughts,” he said.

This kind of advanced solution is a very long way off, said Dr Repova.

“But look at cochlear implants – 40 years ago when they started, we had no idea how it would develop, how widely they would end up being used,” she said, referring to the inner-ear implants used to tackle severe deafness.

“A happy end would be a device implanted in the throat that could talk with the patient’s own voice,” she told AFP.

“It’s realistic: it may not come in a year or even in 10 years, but it’s realistic and we’re on the way.”

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January, 2019|Oral Cancer News|