Oral Cancer News

What University of Toronto researchers are doing to help ‘devastating’ swallowing problems

Source: www.utoronto.ca
Author: Jim Oldfield

We swallow about 600 times a day, mostly without thinking about it. But swallowing involves dozens of muscles and nerves in the mouth, throat and esophagus, and for people who struggle with the process, the results can be devastating.

Malnutrition, dehydration and social isolation are common in people with swallowing trouble. So is depression and aspiration of food that leads to pneumonia. Occasionally, swallowing issues cause choking and sudden death. And a recent U.S. study of hospitalized patients with serious illnesses found that more than half said needing a feeding tube to live was a state equal to or worse than death.

Many conditions can cause swallowing problems: stroke, neurodegenerative diseases such as Parkinson’s, and congenital or developmental conditions such as cerebral palsy and cleft palate. People treated for head and neck cancer often develop problems, sometimes years later; and their numbers are growing as cancer survival rates improve. Estimates on the global prevalence of swallowing disorders, which collectively are known as dysphagia, are about eight per cent – almost 600 million people.

But there is good news. Before 1980, most patients with complex dysphagia got feeding tubes; today, clinicians can offer videofluoroscopy and other bedside tests to better assess swallowing problems, and less invasive therapies that emphasize exercise and posture.

And at the University of Toronto, scientists in the department of speech-language pathology and related fields are starting to answer long-standing questions such as how best to give dysphagia screening tests, which interventions work well for specific conditions, and how to create global standards to talk about and address swallowing issues.

Through research, we may be entering a new era in dysphagia care.

Which approach is better?
More than two-thirds of head and neck cancer patients need a feeding tube for several months, after radiotherapy. They typically get therapy from a speech language pathologist before swallowing problems begin or once symptoms arise. Both methods provide benefits, but the extent of the benefits from each approach is unclear.

Professor Rosemary Martino and her colleagues just launched a study that will provide answers. The US$8.5 million PRO-ACTIVE project will enrol 1,000 patients over five years in Toronto and six other cities across North America.

“The stuation now is what we call clinical equipoise,” says Martino, a professor in the department of speech-language pathology who holds a Canada Research Chair in swallowing disorders. “Both treatment approaches work but we don’t know which is better, and so we can’t know where to invest the most resources. We also know the clinical community is mixed in what they offer patients; this study will hopefully resolve those uncertainties once and for all.”

The researchers will track patients who get both proactive and reactive therapy, then measure and compare their ability to eat and swallow along with other health outcomes up to one year after radiotherapy. They will also parse the effects of each approach in different groups of patients and compare the effectiveness of low- and high-intensity proactive interventions. (Low-intensity therapy is pragmatic, with a focus on exercising oral musculature during meal times and some snacks; high-intensity therapy includes additional exercises between meals.)

“Intensity is both a resource and patient burden issue,” says Martino, whose lab is based at U of T and the Krembil Research Institute in University Health Network. “We know patient adherence to exercise therapy is often low, so we need to make sure we don’t overprescribe and raise the risk that they do nothing. And with better evidence, we can let patients know exactly how much better their swallow will be if they comply.”

The study will engage patients and families, clinicians and policy makers at several points, toward ensuring that new findings are practical and available to patients right away. Study researchers will also use new health informatics and quantitative imaging technology to establish the first international database to compare the effectiveness of swallowing interventions relative to radiation targets and doses. The database, housed by Martino and her team at University Health Network, will support trials to further guide therapy and help preserve the swallowing ability of patients.

A quick and effective screening test
Almost 60 per cent of acute stroke patients have some swallowing impairment. Stroke patients with dysphagia are three times more likely to get pneumonia, and for those with severe dysphagia, the risk of pneumonia is 11 times higher.

Globally, there is a pressing need for a quick and reliable bedside screening tool that can tell clinicians if a stroke patient has dysphagia: Early identification of swallowing problems allows for earlier intervention, which reduces the risk for pneumonia, malnutrition and death while speeding patient recovery and limiting health-care costs.

In the early 2000s, Martino’s lab developed a screening test called the Toronto Bedside Swallowing Screening Test (TOR-BSST), a simple one-page tool that only takes 10 minutes to administer and that allows clinicians to determine if a patient has a swallowing problem. In 2009, they published results from a trial of more than 300 stroke patients that showed the test had an accuracy rate of over 90 per cent. It was a practice-changing study.

The lab quickly set up an online training module and began to teach health professionals in Toronto and across Canada and the U.S. how to deliver the test. The tool has now been translated into six languages and is being adopted around the world, most recently in Japan and Brazil. “The TOR-BSST is really a Canadian success story, and we’re now validating this tool in critically ill cardiac patients who have been intubated for one day or more”, says Martino.

Almost 400 clinicians globally have used the TOR-BSST. Martino and her colleagues continue to study new ways of delivering the test and they expect further results later this year.

Why making food easy to swallow is hard
A key treatment for dysphagia is diet-texture modification. Many patients find that soft or liquified foods are easier to swallow, but the best consistency for each patient is highly variable. As well, there is no globally accepted way to name and describe texture-modified foods, which has led to poor communication among patients, caregivers and families, and undermined treatments.

In 2013, international experts from several health professions came together to develop a common terminology for texture-modified foods and instructions for simple methods to test food and drink consistency. The group – the International Dysphagia Diet Standardisation Initiative (IDDSI) – published a framework in 2015, and soon after several countries made implementation plans.

New Zealand became the first country to adopt IDDSI in January, and Canada and the U.S. are on track to implement early next year.

“For people with swallowing issues, food and liquid are like medication, and they come with some of the same risks. Getting diet texture wrong can kill,” says Catriona Steele (pictured left), who is a professor in the department of speech-language pathology, an IDDSI board member and a senior scientist at the Toronto Rehabilitation Institute in University Health Network. “Inside the hospital, we don’t treat the kitchen with the same reverence as the pharmacy.”

Steele says the IDDSI framework will bring much more attention to dysphagia diets, but that kitchens and food manufacturers that prepare food for dysphagia patients in Canada have a lot of work to do before roll-out. For example, labels on commercially available products need to change. Moreover, there are still major knowledge gaps regarding which consistencies are best for patients with different conditions.

“Liquid behaves one way in a person with an intact system but may not behave the same in someone with stroke or head and neck cancer,” says Steele, whose lab has studied the physiology of swallowing since 2003. “So clinically, people have been making educated guesses. We’ll collect data for IDDSI on particular measurements in specific conditions to guide clinicians down the road.”

In another project, Steele and colleagues at the University of Waterloo recently looked at nutrition in seniors at 32 long-term care facilities in Canada. The study, called Making the Most of Mealtimes, found that texture-modified foods contribute to malnourishment, in part because people eat less of them and puréeing changes nutrient density.

“People prescribe these liquids with good intentions in terms of safety, but they might be creating a negative cycle that leads to malnutrition,” says Steele, although she points out that researchers are trying to improve the nutrition of these foods through supplements.

Another challenge in seniors and others with dysphagia is the emotional aspect of food.

“We all love to eat, so dietary changes can be very threatening to people. And there are many possible reasons for negative emotions around food,” says Steele. “Early in my career, I worked with Holocaust survivors, for example, and modifying food texture had particularly negative associations for them. So we need to do this carefully and only when justified, and that’s not the standard of care at present.”

A guide to treating the young
Children with swallowing problems can be especially hard to diagnose, in part because the potential reasons for feeding issues are many: feeding aversion secondary to gastrointestinal reflux, sensory issues in autism, problems with muscle weakness or co-ordination in the face or neck, cardiac or respiratory conditions, and lack of appetite from medications, to name a few.

Moreover, many strategies that clinicians use in adults will not work in the pediatric population for developmental reasons. For children with developmental difficulties, swallowing problems are very common and upsetting for families. Up to 80 per cent of these children have some kind of feeding or swallowing impairment.

Treatment for children with developmental challenges is complex, and often demands a team of health professionals that may include a physician, speech language pathologist, developmental paediatrician, occupational therapist, physical therapist, dietitian and nurse.

The clinical feeding and swallowing team at Holland Bloorview Kids Rehabilitation Hospital provides comprehensive expertise to patients with developmental challenges at the hospital. But they also share their knowledge with colleagues at community hospitals, clinics and individual community practitioners, who often face a knowledge gap when trying to address dysphagia in children with developmental issues.

To that end, the swallowing team at Holland Bloorview and the hospital’s Evidence to Care group recently developed a handbook, Optimizing Feeding and Swallowing in Children with Physical and Developmental Disabilities: A Practical Guide for Clinicians. The handbook provides a hierarchical and integrated approach to guide practice, and highlights key considerations clinicians might face.

“There was a lack of clear summaries of the scientific evidence available across disciplines that presented information in an accessible, efficient way for a broad group of community clinicians who may need to care for children with feeding and swallowing impairments,” says Deryk Beal, an assistant professor in U of T’s department of speech-language pathology and clinician scientist at Bloorview Research Institute.

The guide has been a huge success. Viewers have downloaded it more than 4,600 times since it appeared online in June last year, in more than a dozen countries and every Canadian province. The University of Montreal made it required reading for a third-year occupational therapy course, and a survey by Holland Bloorview staff found many users praised the guide for its clarity and relevance to practice.

Clinicians say they use the guide in several ways – as a quick-reference tool when seeing patients, when sharing knowledge with colleagues, and for on-boarding new staff and teaching students. Many users like the guide’s interprofessional focus, which enables them to better understand the perspectives and treatment options that professionals in other fields can bring to cases.

“We know feeding and swallowing is a specialized area of medical care and a lot of people working in the community may not have received specific training in some elements of the care they’re providing,’’ says Andrea Hoffman, an assistant professor in the department of pediatrics and developmental pediatrician at Holland Bloorview. “This handbook helps give them a framework to gather information and determine the important elements of the assessment from a range of disciplines, so they can make the best recommendations and most appropriate referrals to provide optimal care.”

Hoffman and her colleagues recently published two quick-reference handouts based on the guide, and also plan to create client-centred resources for families.

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April, 2018|Oral Cancer News|

Woman’s missing jaw regrown by 9 cm after cancer

Source: www.bbc.com
Author: staff

A woman who lost her jaw to cancer has had it regrown from her own skin and bone.

Val Blunden had the bottom of her mouth and chin destroyed by cancer more than two years ago. The 55-year-old was left unable to eat, drink and talk, taking early retirement from her job as a postwoman. Using new treatment, surgeons from Nottingham and Wolverhampton have reconstructed her jaw by “stretching” her own tissue and bone around a frame.

Known as distraction osteogenesis, the process has been around for a number of years but never been used in this way before, Dilip Srinivasan, maxillofacial surgeon at Nottingham University Hospitals Trust, said. A frame built at Queen’s Medical Centre in Nottingham has acted as “scaffolding”, and since an operation in January the jaw has grown 9cm.

It is hoped the final surgery to remove the frame will take place in May.

Ms Blunden, from Wolverhampton, first found a lump underneath her tongue in January 2015 and following diagnosis has had glands, chin, lower lip and part of her tongue removed. After two previous attempts to reconstruct her jaw using skin grafts failed, and with her being unable to use a prosthetic replacement, she hopes the procedure will improve her life.

“Having lived like this for two years I’d begun to accept that this is how life was going to be, but now I’m so much more hopeful for a different future,” she said.

Mr Srinivasan said: “We have been able to achieve this in a few operations before, but we’d never attempted it on a patient missing bone, skin and muscles.

“When there’s no jaw, there’s no shape to follow, and if there’s no shape to follow everything will grow in a straight line.”

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April, 2018|Oral Cancer News|

HMB/Arg/Gln does not reduce oral mucositis incidence in head and neck cancer

Source: www.oncologynurseadvisor.com
Author: James Nam, PharmD

The addition of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine (HMB/Arg/Gln) to opioid-based pain control (OBPC) and oral care programs does not effectively prevent chemoradiotherapy (CRT)-induced oral mucositis (OM) in patients with head and neck cancer (HNC), according to a study published in Supportive Care in Cancer.

Chemoradiotherapy with a cisplatin-based chemotherapy regimen is the standard of care for patients with HNC, but is associated with a high incidence of CRT-induced OM. OBPC and oral care programs are insufficient in reducing OM incidence; there is a need for additional interventions to prevent and treat OM.

For this phase 2 study, researchers treated 35 patients with HNC scheduled to receive definitive or postoperative cisplatin-based CRT with oral or percutaneous endoscopic gastrostomy-delivered HMB/Arg/Gln; all patients underwent OBPC and oral care programs.

Results showed that 45.7% (16) of patients developed symptomatic or functional grade 3 or worse OM. Grade 1 or less OM occurred in 51.1% of patients at 2 weeks and in 82.9% of patients at 4 weeks postradiotherapy completion.

Clinical examination, however, revealed that 28.6% (10) of patients developed grade 3 or worse OM, and the incidence of grade 1 or less OM was 80.0% and 100% at 2 weeks and 4 weeks after completing radiotherapy, respectively.

The most frequently reported adverse events included diarrhea and an increase in blood urea nitrogen, but were easily managed with standard care.

Evidence from the study demonstrates that HMB/Arg/Gln does not effectively decrease OM incidence; however, the authors concluded that “the benefit of HMB/Arg/Gln should not be neglected given the findings of clinical examinations and the rapid recovery from severe OM.”

Reference
1. Yokota T, Hamauchi S, Yoshida Y, et al. A phase II study of HMB/Arg/Gln against oral mucositis induced by chemoradiotherapy for patients with head and neck cancer [published online April 7, 2018]. Support Care Cancer. doi: 10.1007/s00520-018-4175/4

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April, 2018|Oral Cancer News|

The Society for Immunotherapy of Cancer highlights immunotherapy during Oral, Head and Neck Cancer Awareness Week

Source: www.prweb.com
Author: press release

The Society for Immunotherapy of Cancer (SITC) recognizes Oral, Head and Neck Cancer Awareness Week, April 8-15, 2018, in an effort to highlight targeted immunotherapy to treat patients with these types of cancer.

To educate and guide patients, SITC provides informative and engaging online education dedicated to cancer immunotherapy through SITC Cancer Immunotherapy connectED. Two head and neck cancer-specific resources are available on SITC connectED:

Beyond Chemotherapy for Treatment of Head and Neck Cancer: Developed for patients with head and neck cancers and their care partners, the goal of this online class is to learn about treatment options for the newly diagnosed, treatment after chemotherapy, and questions to ask the patient’s healthcare team.

Understanding Cancer Immunotherapy Patient Resource Guide: This guide provides current, medically accurate information on cancer (including head and neck cancers) – intended for patients and caregivers to outline available cancer immunotherapy options, the role of the immune system in this type of cancer treatment and what to expect while undergoing treatment. (free registration required)

Aiming to make cancer immunotherapy a standard of care for cancer patients everywhere, these SITC connectED resources educate and guide patients on immunotherapy treatment options for head and neck cancer. For more information, visit the SITC website at sitcancer.org.

About SITC
Established in 1984, the Society for Immunotherapy of Cancer (SITC) is a nonprofit organization of medical professionals dedicated to improving cancer patient outcomes by advancing the development, science and application of cancer immunotherapy and tumor immunology. SITC is comprised of influential basic and translational scientists, practitioners, health care professionals, government leaders and industry professionals around the globe. Through educational initiatives that foster scientific exchange and collaboration among leaders in the field, SITC aims to one day make the word “cure” a reality for cancer patients everywhere. Learn more about SITC, our educational offerings and other resources at sitcancer.org and follow us on Twitter, LinkedIn, Facebook and YouTube.

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April, 2018|Oral Cancer News|

Be your own advocate

Source: www.wvnews.com
Author: Mary McKinley

The importance of dental care goes beyond cavities — it’s also about preventing cancer. The week of April 8 is National Oral, Head and Neck Cancer Awareness Week, and your dentist or dental hygienist may be your first line of defense against oral cancer.

More than 50,000 Americans are expected to be diagnosed with oral or oropharyngeal cancer (cancer of the back of the throat, including the base of the tongue and the tonsils) in 2018, and 350 will be diagnosed in West Virginia alone.

Routine dental exams can detect cancer or pre-cancers during the early stages. If you notice a persistent sore or pain, swelling or changes in your mouth, or red or white patches on the gums, tongue, tonsils or lining of the mouth, visit a doctor or dentist so they can examine your mouth more closely.

Some people diagnosed with oral cancer have no risk factors, so it’s important for everyone to keep those dental appointments.

If you use tobacco, drink alcohol in excess, or have the human papillomavirus (HPV), you have an increased risk for oral cancer. Oral cancer is more common in older adults, particularly men, but oropharyngeal cancer is on the rise in middle-aged, nonsmoking white men between the ages of 35 and 55. The majority of these types of cancer cases are caused by HPV.

Take charge of your health and reduce your risk of oral cancer. If you smoke or chew tobacco, quit now (it’s never too late). Moderate your alcohol consumption to no more than one drink a day for women or two for men.

If you have children, make sure they receive the HPV vaccine, which is recommended for all girls and boys ages 11 and 12; a “catch-up” vaccine is also available for young women up to age 26 and most young men up to age 21.

You can be your own best advocate. Check the inside of your mouth in the mirror each month, and speak up to your dentist or dental hygienist if you notice any changes that concern you.

Ask about cancer screenings when making your dental appointments. And to learn more about cancer prevention, be sure to visit www.preventcancer.org.

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April, 2018|Oral Cancer News|

April is National Oral Cancer Awareness Month

Source: www.prnewswire.com
Author: press release

April marks oral cancer awareness month, and this year the Academy of General Dentistry is calling on dentists and patients to increase dialogue and screenings to address the growing number of oral cancer cases.

Nearly 50,000 Americans are diagnosed with oral cancer each year and of those diagnoses, roughly a fifth will result in death*. Oral cancer cases have increased in the past two decades, linked to the spread of oral HPV**.

“Oral cancer is often called the silent killer because it silently invades the body during early stages, and patients don’t notice symptoms until it is quite advanced,” said Manuel Cordero DDS, CPH, MAGD, president, Academy of General Dentistry. “Vaccination against HPV is the first line of defense for young people, but screenings are critical for the broader population. Most people don’t realize screenings are part of their six-month dental checkups, and that needs to change.”

In a 2017 survey, the Academy of General Dentistry found that only 25 percent of Americans view their dentist as an expert on oral cancer screenings – even though screenings are part of regular checkups.

“It’s time for patients and dentists to talk more openly about oral cancer, starting with screenings, as well as preventative measures like HPV vaccination and not using tobacco,” added Dr. Cordero.

For more information on oral cancer awareness, and to schedule a dental checkup with screening, visit: www.agd.org/agd-foundation/our-programs/oral-cancer-screenings.

* https://oralcancerfoundation.org/facts/

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April, 2018|Oral Cancer News|

Accurately identifying aggressive head and neck cancers

Source: www.eurekalert.org
Author: press release

The Case Western Reserve-led research team will analyze computerized images of tissue samples for patterns which could become “biomarkers,” or predictors, for determining relative risk for recurrence in one particularly common type of head and neck cancers.

Those tumors, known as oropharyngeal cancers, occur primarily at the base of the tongue and in the tonsils.

Currently, however, oncologists tend to treat all of these tumors with the same aggressive level of therapy. This is the case even though many of the oropharyngeal tumors which are caused by the human papilloma virus (HPV) tend to have favorable outcome-regardless of treatment-while another subset of the tumors progress and metastasize, or spread.

“Right now, it’s a one-size-fits-all therapy for all of these patients with HPV head and neck cancers,” said Anant Madabhushi, MD, the F. Alex Nason Professor II of Biomedical Engineering, founding director of the CCIPD at the Case School of Engineering and primary investigator in the new research.

“There are currently very few validated biomarkers and approaches that are accurate enough to be able to identify which of these cancers are more aggressive or which ones are less aggressive,” he said. “That has limited the ability of clinicians to even hold clinical trials to find out if they can de-escalate therapy for some of these patients-or who needs more aggressive therapy.”

The National Cancer Institute (NCI) recently awarded a $3.15 million, five-year academic-industry partnership grant to Madabhushi and his team to pursue the research and build toward establishing those clinical trials.

Co-primary investigator on the grant is Vanderbilt University’s James Lewis Jr., MD, whose specialty is head and neck pathology, while Cleveland Clinic’s Shlomo Koyfman, MD, and David Adelstein, MD, are co-investigators with expertise in radiation and medical oncology.

Additionally, Pingfu Fu, an associate professor of population and quantitative health statistics at Case Western Reserve, brings expertise in biostatistics. Cheng Lu, a senior research associate in CCIPD is also involved with the project.

Madabhushi’s team is again working with Mark Lloyd, MD, of industry partner Inspirata Inc., the Florida-based company also teaming up with the lab on studies of breast and lung cancer-work supported by more than $6.3 million in NCI funding.

The team presented its data at the 2018 United States and Canadian Association of Pathology (USCAP) meeting in Vancouver this month and has generated data to suggest that the approach could soon become a clinically actionable tool.

Initial results on almost 400 oropharyngeal cancer patients suggests that the technology is independently prognostic of disease progression-meaning that it could stand alone in helping clinicians figure out how aggressive the disease is and then make a more informed decision on how aggressively to treat the cancer.

“In those cancers, they’ve established whether you can modulate your therapy based on the risk profile for those tumors,” Madabhushi said. “But in head and neck, clinicians might have a sense that there are different risk profiles for different patients, but nobody knows for certain. We want to change that by giving them the risk stratification tools to better help the patient.”

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March, 2018|Oral Cancer News|

A better understanding of how genetics influences responses to mouth cancer drugs could lead to improved treatment

Source: medicalxpress.com
Author: provided by Agency for Science, Technology and Research (A*STAR)

A single letter DNA mutation is a big determinant of whether patients with advanced oral cancer respond to treatments. Researchers from the National Cancer Centre Singapore (NCCS) and A*STAR who uncovered the mechanisms behind this effect hope their findings will help doctors target treatment more effectively.

Oral squamous cell carcinoma (OSCC) is characterized by the uncontrolled growth of thin, scale-like squamous cells in the outer layer of the mouth. Only around 50 per cent of patients who are treated through surgery or radiotherapy are cured, and the average duration of survival of those with advanced OSCC that recurs following treatment is just 6 to 9 months.

Epidermal growth factor receptors (EGFRs) play important roles in driving the progression of some OSCCs. Drugs that target them, however, only work in a small number of patients.

A 2012 clinical trial led by Daniel Tan at NCCS and A*STAR’s Genome Institute of Singapore had found that the EGFR-blocking drug gefitinib worked well in two patients with two copies of the EGFR coding gene with an adenine (A) nucleobase in place of the more common guanine (G) at a particular location.

More recently, tests by Gopal Iyer, also at NCCS, and Tan showed that OSCC patient-derived cells with the above A/A genotype were sensitive to gefitinib and erlotinib, another EGFR blocker. Those with the G/G or G/A variants exhibited resistance to the drugs.

Editing the DNA of the G/G genotype cells to become G/A at the same location increased their sensitivity to the drugs 70-fold. “We were pretty surprised it had such a dramatic effect,” says Iyer.

The genetic mutation occurs in a section of DNA that modulates the stability of a long non-coding RNA (lncRNA) known as EGFR-AS1. Gene expression tests showed that levels of this lncRNA were significantly higher in G/G genotype cells than in A/A cells.

When cells with the G/G genotype were exposed to small interfering RNAs that reduced their production of EGFR-AS1, their sensitivity to EGFR-blocking drugs increased significantly.

They also found that the tumors of seven patients with the A/A genotype shrank following treatment with EGFR-inhibiting drugs.

While the mechanism underlying this effect is not fully understood, the group has demonstrated that cells of the G/A and A/A genotypes produced higher ratios of one of four variants of EGFR relative to another, and that EFGR-AS1 helps mediate this difference.

Iyer said that new RNA-interference therapies could be developed to target cancers dependent on EGFR signaling. The group is conducting a larger human trial to better understand the biomarkers that could provide for improved targeting of existing treatments.

Source:
Daniel S W Tan et al. Long noncoding RNA EGFR-AS1 mediates epidermal growth factor receptor addiction and modulates treatment response in squamous cell carcinoma, Nature Medicine (2017). DOI: 10.1038/nm.4401

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March, 2018|Oral Cancer News|

Management strategies for oral potentially malignant disorders

Source: www.medscape.com
Author: Joel M. Laudenbach, DMD

Oral potentially malignant disorders (OPMDs) include oral leukoplakia (OL), oral erythroplakia, oral submucous fibrosis, oral lichen planus, proliferative verrucous leukoplakia, and actinic keratosis. Once an OPMD has been clinically diagnosed, execution of management strategy is critical. When formulating the strategy, healthcare providers should consider histopathology, lesion characteristics (ie, surface texture, unifocal, multifocal), lesion location in the mouth (ie, tongue, floor of mouth), patient risk factor assessment, and a detailed medical/cancer history.

In this newly published article, Nadeau and Kerr[1] detail various parameters surrounding evaluation and management of OPMDs. The authors make it clear that OPMDs are challenging, each with their own nuances regarding risk for malignant transformation. For example, when OL is unifocal, nonhomogeneous, nodular, or verrucous, there is a much higher chance of the OL becoming dysplastic (12.63-fold) or demonstrating a focus of carcinoma (8.9-fold) when compared with homogeneous types of OLs.[1]

Provider knowledge of these variables is critical when counseling patients about their diagnosis and management options and when selecting interventions along with follow-up care. Although progression to malignancy is difficult to predict with OPMDs, clinicians can account for multiple risk factors such as smoking/alcohol status, high-risk location in the oral cavity, and size of lesion (>200 mm2) to help formulate a tailored management plan for each patient. Consultation with an oral pathologist to discuss the histologic appearance in the context of specific patient history and lesion characteristics can provide additional perspective and/or recommendations.

Modifiable oral cavity cancer risks related to tobacco and heavy alcohol use should be communicated to patients with OPMDs so that they are able to make changes that may lead to regression/disappearance of certain lesions such as OL. Providers confronted with patients who use tobacco and/or heavy alcohol can integrate recommendations for cessation of tobacco[2] and alcohol[3] because they are both established, independent, causative agents for oral cavity cancer and OPMDs.

Available treatment strategies for OPMDs include surgical removal/ablation, photodynamic therapy, and surveillance. The authors make a clear point with supportive studies that traditional surgical excision of dysplastic OPMDs may decrease malignant transformation (MT) risk, yet it does not fully eliminate that risk and, in some instances, has not changed the MT risk when compared with surveillance alone. Appropriate surgical margin identification for OPMDs is clinically challenging. The authors note that smaller excisional margin sizes (1-2 mm) without marginal histologic assessment are common surgical management goals for OPMDs.[1]

Viewpoint
Nadeau and Kerr carefully outline updated considerations for all OPMDs. Healthcare providers involved in screening, diagnosing, referring, and/or managing patients with OPMDs should be well versed in standards of care, including baseline biopsy goals, tobacco/alcohol cessation, currently available interventions, and surveillance care.

Clinicians should also develop a local team of practitioners who are experts in diagnosis and management of OPMDs to help patients obtain the best opportunity for positive outcomes. I encourage readers with interest to retrieve and review the full article by Nadeau and Kerr as a strategy to update your knowledge base and to continue to improve overall morbidity, mortality, and survival rates related to OPMDs.

References:
1. Nadeau C, Kerr AR. Evaluation and management of oral potentially malignant disorders. Dent Clin North Am. 2018;62:1-27.

2. US Preventive Services Task Force. Final recommendation statement. Tobacco smoking cessation in adults, including pregnant women: behavioral and pharmacotherapy interventions. September 2015. https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/tobacco-use-in-adults-and-pregnant-women-counseling-and-interventions1 Accessed March 1, 2018.

3. US Preventive Services Task Force. Final recommendation statement. Alcohol misuse: screening and behavioral counseling interventions in primary care. May 2013. https://www.uspreventiveservicestaskforce.org/Page/Document
/RecommendationStatementFinal/alcohol-misuse-screening-and-behavioral-counseling-interventions-in-primary-care Accessed March 1, 2018.

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March, 2018|Oral Cancer News|

The Sate of Liquid Biopsy

Author:Pam Harrison
Date: March 5, 2018
Source: Medscape.com

So called “liquid biopsies” — which can detect circulating tumor DNA (ctDNA) in blood samples — are not yet ready for prime time in the diagnosis or management of early-stage or advanced solid tumors, a new expert review concludes.

These assays are also not useful, outside of clinical trials, for monitoring patients for minimal residual disease following definitive treatment of cancer, nor for cancer screening, the expert review concludes.

The review was prepared jointly by the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) and was published online March 5 in the Journal of Clinical Oncology.

“This is an area of great interest to both pathologists and oncologists, [and] it’s also an area where we see a lot of commercial advertisement and a lot of enthusiasm from the public,” Jason Merker, MD, PhD, cochair of the expert panel, who was representing the CAP, said in a statement.

“We thought it was a good time to look at the literature and take an evidence-based approach to various uses for ctDNA assays,” he added.

“Like all new things in medicine, the use of ctDNA assays in routine cancer care requires evidence of clinical utility. At present, there is insufficient evidence of clinical validity and utility for the majority of ctDNA assays in advanced cancer, including those that interrogate a panel of genes,” said Daniel F. Hayes, MD, coauthor of the review, who was representing ASCO.

“What is promising is that this area of research is rapidly evolving, so there should be enough evidence soon to formulate evidence-based guidance for a variety of clinical scenarios,” Hayes suggested.

Review Based on Literature Review

For the review, panel members identified 77 relevant articles in the literature. They limited their analysis to variants in ctDNA for solid tumors and to sequence or copy number variants in DNA.

 

They assessed overall evidence of the ability of a test to reliably detect the variant or variants of interest (analytic validity); whether a test accurately detects the presence or absence of a pathologic state or predicts outcomes for patients (clinical validity); and whether the use of the test improves patient outcomes compared with not using it (clinical utility).

The authors focused largely on the use of ctDNA assays in the setting of metastatic cancer, because that is the area for which there is most evidence. Much less research supports the use of liquid biopsy in other settings.

Advanced Cancer

“Fundamentally, there are two paradigms to demonstrate clinical utility and the adoption of ctDNA as a clinically useful test,” the panel members write.

The most reliable strategy is to conduct a prospective clinical trial designed to evaluate how well the test performs as a stand-alone diagnostic test. However, no such trial has yet been carried out, they write.

The second approach is to assess whether the ctDNA test in question delivers the same information that physicians would seek through tissue genomic evaluation.

“[D]emonstrating that a ctDNA assay has high agreement with tumor tissue genotyping may provide sufficient evidence of utility for ctDNA assays in driving patient treatment decisions,” the panel members explain.

They go on to document how far short ctDNA assays fall with respect to meeting this high level of agreement.

First, only one polymerase chain reactin–based ctDNA test has been approved by the US Food and Drug Administration and the European Medicines Agency. That test is the COBAS assay for the detection of EGFR genetic variants in non–small cell lung cancer (NSCLC).

Another assay is available in Europe for the detection of the KRAS mutation in colorectal cancer (CRC).

“These assays have demonstrated clinical validity but the clinical utility in this setting is based on retrospective analyses,” the panel members point out.

Even in light of these approvals, the panel members note that physicians should continue to rely on tissue sample analysis if nothing is detected on ctDNA testing.

They also point out that ctDNA levels may drop while a tumor is still responding to treatment, and as a result, the sensitivity of the test may be compromised.

As for tumor types other than NSCLC and CRC, there is limited evidence to support the clinical validity of ctDNA analysis, the panel members conclude.

The clinical utility of assays developed for the detection of other potentially targetable variants, such as BRAF in melanoma, is not yet established, they add.

Further confounding the diagnostic potential of ctDNA testing is the fact that advanced cancers may be “genetically heterogeneous.”

Although ctDNA tests may be able to pick up subclonal variants in cancer, these variants may not predict how well patients will respond to treatments that theoretically target the variant.

“[S]ubclonality may undermine the clinical utility of ctDNA assays,” the panel members state.

 

Monitoring Response to Therapy

Ideally, liquid biopsies could help physicians monitor patients’ response to treatment, as some tumor-associated proteins now enable them to do.

This, too, remains a challenge, because quantifying changes in ctDNA over time is not as simple as determining whether or not a variant is present. Nor has the best unit by which to measure DNA burden been established.

“Correlations between changes in ctDNA levels and tumor responses or outcomes have been demonstrated in small proof-of-principle studies in a variety of cancer types,” the panel members acknowledge.

“However, currently there is a lack of rigorous evidence on clinical validity, let alone clinical utility, because few large, prospective validation studies have been performed on ctDNA-based monitoring,” they conclude.

 

Use to Monitor Residual Disease

Researchers expressed hope that after curative treatment of a solid tumor, ctDNA assays could be used to monitor patients for minimal residual disease, much as is done in hematogic malignancies using assays to detect leukemic cells in blood following completion of chemotherapy.

However, there is not enough evidence to support the ability of ctDNA tests to detect low levels of minimal residual disease in a manner similar to assays used in the management of diseases such as leukemia, the panel members conclude.

Moreover, “[t]he false-negative rate of ctDNA analysis in…patients who relapse without ctDNA being detected and the false-positive rate [in] patients who do not relapse despite the ctDNA assay being positive have not been established sufficiently for any assay,” they caution.

There is also no evidence that treatment based on detection of ctDNA improves patient outcomes, a major metric of clinical validity.

Screening for Cancer

In an ideal world, ctDNA tests could be used in the early detection of cancer in patients who have no signs of disease.

However, the feasibility of using ctDNA tests to screen asymptomatic individuals has not been demonstrated.

“[D]iagnosing the presence of cancer in a patient without cancer, and determining tissue of origin, have not been established,” the authors point out.

There is also a risk that such tests might be positive for cancers in cases in which none exists and thus lead to overdiagnosis. Currently, overdiagnosis is a major problem with, for example, mammography in breast cancer and prostate-specific antigen screening for prostate cancer, the panel members observe.

Dr Merker has served as a consultant to or in an advisory role for Bio-Rad Laboratories, Rainbow Genomics, and Genoux and has received patents or royalties or has other intellectual property in the measurement and monitoring of cell clonality. Dr Hayes owns stock or has other ownership interests in OncImmune and InBiomotion and has served as a consultant or as an advisor to Cepheid. He has also received research funding, mostly for his institution, from AstraZeneca, Puma Biotechnology, Pfizer, Eli Lilly, Merrimack Pharmaceuticals, Parexel, and Menarini Silicon Biosystems (aka Veridex/Johnson & Johnson). He also holds a number of patents and receives royalties for some of them.

 

 

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March, 2018|Oral Cancer News|