radiotherapy

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.

April, 2018|Oral Cancer News|

UK cancer patient receives new jaw thanks to 3D printing

Source: http://www.3ders.org/
Author: staff

3D printing techniques are being adopted with increasing regularity in surgery of all kinds, and more and more patients are seeing a hugely improved quality of life thanks to the unique benefits of the technology. The most recent success story took place in the UK, where a patient’s jawbone was entirely reconstructed using bone from his leg. The pioneering surgical procedure made use of 3D printing at various different stages.

Stephen Waterhouse was diagnosed with throat cancer eight years ago, and underwent chemotherapy and radiotherapy in order to fight it. The treatments were a great success and his cancer went away, but they had an unfortunate side effect. His jawbone had started to crumble, and emergency surgery was required before it completely disintegrated. The 53-year-old was taken to Royal Stoke University Hospital, which had purchased a new 3D printer just two years previously.

Costing the hospital trust around £150,000 (about $188K), the machine is the only one of its kind in the country, and was a crucial part of the effort to save the patient’s jawbone. A 3D model was designed from a scan of his remaining intact jaw and printed out as a mold, which was then used to reconstruct the jaw using bone taken from his fibula. The operation lasted around 12 hours and was a great success.

According to Daya Gahir, consultant in maxillofacial and head and neck surgery, the hospital does “at least 40 major head and neck reconstructions per year. Around 10 to 15 cases will be done in this way using the printer.” The procedure is very intricate, and the hospital’s purchase of the 3D printer has revolutionized the way his team operates. “Some of the leg bone was taken then reshaped, as you have to replace bone with bone. We took away some of the skin from the leg as well and replanted it back into the neck. A face is not easy to reconstruct, it is intricate.”

New software for the 3D printer was developed last year, which allows the whole process to be planned and carried out within the hospital. Without this, Stephen may have had to travel to Germany for the operation to be completed, according to Gahir. Using the 3D printer in this way saves a lot of time and effort for patient and medical team alike, as well as cutting costs. Around £11,000 is saved for each case by carrying out the whole surgical process on-site.

Stephen is still in recovery and has praised the care he is receiving from staff, as well as the effectiveness of the surgery. “I am so pleased with the results,” he says, “you can’t tell the difference between the two sides of my mouth.”

March, 2017|Oral Cancer News|

Artificial larynx implant helps throat cancer patient breathe and speak

Source: www.ctvnews.ca
Author: staff

Sixteen months after receiving an artificial larynx, a 56-year-old French man suffering from throat cancer can now whisper and breathe normally. A report published this week in the New England Journal of Medicine considers this to be a significant first achievement.

Thanks to the implant, a 56-year-old throat cancer patient can now whisper and breathe normally. © ChrisChrisW / Istock.com

Thanks to the implant, a 56-year-old throat cancer patient can now whisper and breathe normally. © ChrisChrisW / Istock.com

This is the first time that doctors have observed a patient with the implant long term recover functions such as breathing and speaking after the complete removal of the larynx. Thanks to an artificial voice box, implanted in 2015 at France’s Strasbourg-Hautepierre university hospital, the 56-year-old Frenchman, who lives in Alsace, can now whisper in a comprehensible manner and breathe normally.

The patient has also recovered his sense of smell, which was damaged by the removal of the larynx. Other than the vocal cords, the larynx features an upper valve, called the epiglottis, which closes when food passes down the throat to prevent it from entering the windpipe.

The prosthetic larynx was developed by a French company called Protip Médical. It consists of a rigid titanium and silicone structure replacing the larynx and a removable titanium part that mimics the function of the epiglottis.

The only problem that remains unresolved in the implant is the function of the epiglottis. As a result, the patient coughs from time to time when eating, as food accidentally enters the windpipe. However, the surgeons still consider the functioning implant a highly satisfactory achievement.

The current procedure used to return voice function to throat cancer patients involves puncturing the throat to insert a valve allowing air to pass from the windpipe to the esophagus.

A few doubts remain about the long-term effectiveness of the implant. For example, blockages caused by dried out mucus and secretions from the lungs and nose could be a risk. Another concern is the risk of rejection, particularly in cancer patients who have undergone radiotherapy or chemotherapy treatments.

As for patient comfort, further testing will establish how the mobility of the patient’s neck is affected by the presence of a rigid tube in the throat.

“This implant is constantly evolving and the next patients will benefit from substantial improvements,” notably to improve the passage of food down the throat, said lead researcher Nihal Engin Vrana.

Each year more than 12,000 new cases of throat cancer are diagnosed in the U.S.. Larynx transplants remain extremely rare worldwide and are generally used in cases unrelated to cancer, which represent a small majority.

Source: The report is published in the New England Journal of Medicine.

January, 2017|Oral Cancer News|

Google and UCLH to develop AI to improve cancer therapies

Source: www.phgfoundation.org
Author: Julian Harris

Google’s Artificial Intelligence research group announced a new partnership with University College London Hospitals, applying machine learning to radiotherapy treatment for head and neck cancer.

Abstract, Electronic circuit network grunge background

The new partnership is the third since the launch of DeepMind’s health division in February 2016.

The partnership aims to assist clinicians in the segmentation process – designating which areas of the body to target with radiotherapy – which in the case of head and neck cancer is highly time consuming, taking around four hours. The agreement will give DeepMind access to the anonymised scans of around 700 patients, as well as the expertise of UCLH’s world leading team at their specialised head and neck cancer centre.

Google DeepMind hopes to utilise machine learning to make the planning of radiotherapy treatment more efficient and reduce the duration of the segmentation process. Ultimately , clinicians will still be responsible for deciding on treatment plans, but the reduced workload will free up their time to focus on patient care.

If successful, the team hope that they will be able to adapt their segmentation algorithm to other parts of the body and other cancers which can also be treated with radiotherapy.

Machine learning continues to be a promising new area of health technology, with the potential to provide novel solutions to a range of problems in healthcare. In the UCLH press release, the Co-Founder of DeepMind, Mustafa Suleyman said that “this real-world application of artificial intelligence (AI) technology is exactly why we set up DeepMind… We hope this work could lead to real benefits for cancer patients across the country and for the clinicians who treat them.”

September, 2016|Oral Cancer News|

Follow-up by advance practice nurses improves care for patients with head, neck cancer

Source: www.healio.com
Author: Anthony SanFilippo

The launch of an advance practice nurse outpatient follow-up clinic improved symptom management for high-risk patients with head and neck cancer following radiation therapy, according to findings from a study conducted at Cleveland Clinic. This initiative led to fewer ED visits and hospital admissions, results showed.

“These results are significant as they suggest more intensive follow up in high-risk head and neck patients can improve patient outcomes,” Bridgett Harr, CNP, of the department of radiation oncology at Cleveland Clinic, told HemOnc Today. “This intensive symptom management is an important role [advance practice nurses (APNs)] can fill in this and other patient groups by providing consistent, proactive management of symptoms during recovery from treatment. Our study suggests this will lead to improved patient experience, in addition to a reduction in cost to both the patient and health care system as a whole.”

Patients with head and neck cancer often undergo radiotherapy or chemoradiotherapy, and many experience debilitating side effects that require ED management or admission to the hospital. In 2014, an APN-led clinic was launched to focus on the acute rehabilitation of patients with head and neck cancer undergoing these therapies.

Harr and colleagues sought to evaluate the outcomes and incidence of adverse events among patients treated at an APN clinic compared with historical outcomes.

The analysis included data from 25 high-risk patients with head and neck cancer who received care post-treatment at an APN clinic and 24 patients who received standard follow-up care identified using a database. Clinic patients were seen 2 to 4 weeks after treatment and then every 2 to 4 weeks thereafter until their symptoms stabilized. Standard follow-up patients were seen on average between 4 to 6 weeks after treatment and then not again until 3 months post-treatment.

Patients were considered high risk if they had limited social support (35%), resided in a nursing home (16%), required multiple hydrations during treatment (18%), underwent stereotactic body re-irradiation (15%) and/or required a feeding tube (16%).

Ninety percent of patients had stage IV or recurrent cancer. Primary tumor sites included oropharynx (47%), oral cavity (16%), larynx/hypopharynx (12%) and other (25%).

All patients underwent stereotactic body radiation therapy or intensity-modulated radiation therapy. Fifty-five percent of the patients received chemoradiotherapy with either a cisplatin-based regimen (81%) or cetuximab (19%), and 45% of the patients received radiation therapy alone.

Patients in the APN clinic were seen almost twice as often as those in the standard follow-up group (median, 2 vs. 1.2 visits).

Eighteen patients experienced 26 adverse events that required either a visit to the ED or hospital admission. Six of those patients (33%) were seen in the APN clinic, whereas 12 patients (67%) were from the standard follow-up cohort.

“Not only is there greater patient satisfaction when being managed in an outpatient setting, it is more cost-effective to avoid emergency room or hospital admissions,” Harr said in a press release.

The benefits of the APN clinic appeared more substantial among patients who received radiation alone. Significantly fewer patients treated only with radiation who received their follow-up care at the APN clinic experienced an adverse event in the 90 days immediately after radiation compared with patients who received standard follow-up (60% vs. 16.7%; P = .01).

Researchers observed no difference between the arms for patients who underwent chemoradiotherapy because standard follow-up is also intensive, according to the researchers.

“This study illustrates an important role for APNs in radiation oncology,” Harr said. “APNs are in a unique position to provide more intensive follow-up care, allowing them to better manage the post-treatment symptoms of high-risk head and neck cancer patients.”

November, 2015|Oral Cancer News|

Less Is More for HPV Oropharyngeal Cancer Reduced-intensity regimen clears disease in 86% of cases

Source: www.medpagetoday.com
Author: Charles Bankhead
 

SAN ANTONIO — Less intense treatment of low-risk human papillomavirus (HPV)-related oropharyngeal cancer achieved a high rate of pathologic complete response (pCR) and favorable patient-reported outcomes, a preliminary trial showed.

Overall, 37 of 43 (86%) patients achieved pCR with deintensified chemoradiation, including all but one evaluable primary tumor. The pCR rate was virtually identical to historical rates achieved with standard regimens, according to Bhishamjit Chera, MD, of the University of North Carolina (UNC) at Chapel Hill, and colleagues.

Selected patient-reported adverse events peaked during the first 6 to 8 weeks and then declined thereafter. About 40% of patients required feeding tubes for a median duration of 15 weeks, but no patients required permanent feeding tubes, they reported here at the American Society for Radiation Oncology meeting.

The regimen consists of lower doses of radiotherapy and concurrent cisplatin, administered over 6 weeks. With high-dose therapy, the radiation protocol requires an additional week.

“Though we have limited follow-up, the pathological complete response rate with this reduced-intensity chemoradiotherapy regimen is very high in patients with favorable-risk oropharyngeal squamous-cell carcinoma,” Chera said. “The early quality-of-life measurements are encouraging, particularly the data on swallowing. We are optimistic that these results with reduced-intensity treatment will translate into good long-term disease control with less toxicity.”

The study reflects the current trend and momentum in the management of HPV-positive oropharyngeal cancer, said Zain Husain, MD, of Yale Cancer Center in New Haven, Conn.

“This is the second study to show that de-escalation of therapy might work, and so far, the results really look good,” Husain told MedPage Today. “This is a really important issue, and all of our trials are moving in that direction.”

NRG Oncology (formerly RTOG) has already launched a trial using the UNC regimen, “which gives us a lot of confidence that this is a good regimen,” Husain added. Nonetheless, reduced-intensity treatment remains investigational and should not be used in clinical practice. Randomized clinical trials with adequate follow-up will be required to determine the ultimate role of less intense therapy for HPV-positive oropharyngeal cancer, he said.

Background

HPV-positive oropharyngeal cancer accounts for 60% to 70% of new cases of oropharyngeal cancer in the U.S., and the incidence has continued to rise. In general, HPV-positive disease has a more favorable prognosis as compared with HPV-negative oropharyngeal cancer.

At many institutions, standard therapy for newly diagnosed HPV-positive oropharyngeal cancer consists of total-dose radiotherapy of 70 Gy administered over 7 weeks, and concurrent cisplatin 100 mg/m2 for 3 weeks. The regimen achieves a high rate of pCR but causes substantial toxicity. Given the overall favorable prognosis of HPV-positive oropharyngeal cancer, many specialists have begun to ask whether reduced-intensity treatment might be just as effective with less toxicity.

Chera reported findings from a prospective phase II trial of reduced-intensity chemoradiation for low-risk HPV-positive oropharyngeal cancer. Eligible patients had diagnoses of T0-3, N0-2c, M0 disease associated with minimal or negative smoking history. Treatment consisted of a total radiation dose of 60 Gy administered in 2-Gy fractions daily for 6 weeks, plus concurrent weekly cisplatin 30 mg/m2. The regimen represented a 10-Gy reduction in the usual radiation dose and a 40% reduction in the usual chemotherapy dose, Chera said.

The primary outcome was pCR and was based on experience with usual high-dose therapy, which has been associated with a pCR rate of 87%. Patients undergo biopsy of the primary site 6 to 14 weeks after completing chemoradiation, as well as resection of any initially-positive lymph nodes. Secondary endpoints included toxicity, quality of life (QOL), and clinical outcomes of treatment.

Key Findings

The 86% pCR rate compared favorably with the 87% rate demonstrated by historical data. The overall results included pCR in 40 of 41 evaluable primary tumors (two of which were stage T0 at baseline) and pCR in the neck in 33 of 39 patients (four of whom had N0 status at baseline).

After a median follow-up of 21 months, all 43 patients remain alive and without evidence of disease, including 38 patients who have at least 1 year of follow-up.

Investigators evaluated QOL by means of an instrument developed by the European Organization for Research and Treatment of Cancer (EORTC QLQ H&N-35). Focusing on common adverse effects of chemoradiation for head and neck cancer, Chera noted that the severity score for dry mouth, sticky saliva, and swallowing all increased during the first 6 to 8 weeks, particularly dry mouth and sticky saliva.

The score for dry mouth peaked at about 70 on the 100-point scale and the score for sticky saliva rose to a maximum of about 60. Score for dry mouth remained at about 60 at 12 months, whereas the saliva score declined to about 40. The effect on swallowing was less severe, reaching a maximum of about 20 and then declining to less than 10 at 12 months.

Patient-reported symptoms exhibited a similar pattern as the dry mouth score averaged less than 0.5 (0 to 4 scale) at baseline, increasing to almost 2.5 at 6 to 8 weeks, and then declining to less than 2.0 by 1 year. Patient-rated swallowing difficulty was less than 0.5 at baseline, about 1.0 at 6 to 8 weeks, and slightly less than 1.0 at 1 year.

Physician-rated grade 3/4 toxicity and patient-rated severe/very severe toxicity included mucositis (34%/45%), pain (5%/48%), nausea (18%/52%), vomiting (5%/34%), dysphagia (39%/55%), and xerostomia (2%/75%).

Chera and colleagues have already closed enrollment for another phase II trial that will evaluate a reduced-intensity regimen that makes surgery optional, omits chemotherapy for patients with T1-2 N0-1 disease, and includes patients with as much as a 30 pack-year smoking history but who have a 5-year period of abstinence.

A planned “third-generation” phase II trial will evaluate the feasibility of cancer genetics risk-based stratification of patients and examine more specifically the question of whether reduced-intensity treatment is possible for patients with a >10 pack-year smoking history.

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

October, 2015|Oral Cancer News|

Imaging method has potential to stratify head and neck cancer patients

Source: www.eurekalert.org
Author: press release

Manchester researchers have identified a potential new way to predict which patients with head and neck cancer may benefit most from chemotherapy.

These patients commonly receive pre-treatment induction chemotherapy, before either surgery or radiotherapy, to reduce the risk of disease spread. However the effectiveness of such treatment is reduced in tumours with poor blood flow.

Previous studies have shown that CT scans can be used to assess tumour blood flow. Now researchers at The University of Manchester and The Christie NHS Foundation Trust – both part of the Manchester Cancer Research Centre – have explored the use of MRI scans in predicting which patients would benefit from induction chemotherapy.

Professor Catharine West, who led the study, said: “It’s also important to identify those patients who are unlikely to respond to induction therapy so that we can skip ahead in the treatment pathway and offer them potentially more effective treatments and hopefully improve their outcome.”

The team used an imaging technique known as dynamic contrast-enhanced MRI (DCE-MRI), where a contrast agent tracer is injected into a patient’s vein whilst they have a series of MRI scans taken. This allows scientists and doctors to investigate the blood flow and vessel structure of a patient’s tumour.

They found that the blood flow of a patient’s tumour before they received induction therapy could predict response to treatment. In a paper recently published in the journal Oral Oncology, the group report that those with high tumour blood flow were more likely to respond.

Jonathan Bernstein, a co-author on the paper, said: “Delivery and effectiveness of chemotherapy appears to be better in tumours with higher blood flow. However, amongst those patients with lower measured tumour blood flow, more work is needed to determine those who will and won’t respond.”

Source: ‘Tumor plasma flow determined by dynamic contrast-enhanced MRI predicts response to induction chemotherapy in head and neck cancer’, Bernstein et al. (2015) Oral Oncology

September, 2015|Oral Cancer News|

AstraZeneca joins the world of immunotherapy against cancer

Source: www.youthhealthmag.com
Author: staff

Cancer drug companies have been fighting lately in a completely different and interesting arena: immunotherapy. The competition is indeed heating up that firms such as AstraZeneca are willing to pay millions of dollars for promising treatments. AstraZeneca, through its research company called MedImmune, has just recently announced its decision to purchase a novel drug INO-3112 from Inovio, based in Pennsylvania, for a staggering price tag of $727 million.

INO-3112 is a drug for immunotherapy, a new way of combating cancer by boosting the body’s immune system. This then allows the antibodies and specific cells to fight off the tumor. The treatment may also provide synthetic proteins to boost the body’s fighting chance.

MedImmune believes that with the proper immunotherapy protocol for the patient, conventional methods such as chemotherapy and radiotherapy, which have plenty of serious risks, can now be significantly reduced, if not eliminated. In fact, patients may no longer have to go through surgery, which is a common first-line treatment.

While AstraZeneca already has immunotherapy products in the market, the acquisition of INO-3112 will make it an instrument for combination therapies.

As for Inovio, the drug, which is still not approved, is currently in the advanced stages of the clinical trials. It will be intended for treating head and neck cancers, as well as cervical cancer. While there are already cervical cancer vaccines, they cite the rather poor record of them. Their drug, on the other hand, will work on modifying DNA sequencing that will trigger the manufacture of certain T-cells, which will then curb tumor growth.

So far, MedImmune has already paid its down payment of $27.5 million. The remaining amount will be given as the research and drug reach certain milestones. The company will also pay for the research.

The partnership is also set to increase the revenues of Inovio as it receives a share in the drug’s sale. Both will also be working on cancer vaccines.

August, 2015|Oral Cancer News|

Keytruda doubles efficacy of only targeted therapy for head and neck cancer

Source: www.curetoday.com
Author: Lauren M. Green

The immunotherapy Keytruda (pembrolizumab), in a recent study, proved twice as effective for the treatment of head and neck cancer as Erbitux (cetuximab), the only targeted therapy indicated as a therapy for the disease.

The multisite study offers the largest experience to date of how immunotherapy can be deployed in patients with head and neck cancer, and could change the way the disease is treated. The findings were announced May 29 during the annual meeting of the American Society of Clinical Oncology, a gathering of nearly 30,000 oncology professionals taking place in Chicago.

Keytruda is an antibody designed to disable the protein PD-1 so it cannot do its job of keeping the immune system in check; this allows T cells to become more active in recognizing and fighting cancer cells. In the study, investigators found that the drug produced broad and durable responses in patients with advanced head and neck cancer.

Fifty-six percent of patients in the study experienced some tumor shrinkage with Keytruda, and 86 percent of those patients continued to respond to treatment at data cutoff on March 23, 2015. Keytruda produced an overall response rate (ORR) of 25 percent, and it proved active in both HPV (human papillomavirus)-positive and HPV-negative patients.

“The efficacy was remarkable — pembrolizumab seems to be roughly twice as effective, when measured by response, as our only targeted therapy, cetuximab,” said Tanguy Seiwart, an assistant professor of medicine and associate leader of the head and neck cancer program at the University of Chicago, who presented the results in a press briefing during the ASCO meeting. “We have high hopes that immunotherapy will change the way we treat head and neck cancer.”

Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) has a poor prognosis with a median overall survival (OS) of 13 months in patients treated in the first-line setting, and six months in previously treated patients. Previously treated patients made up the majority of the population of the study, which built on earlier findings from the KEYNOTE-012 study (NCT01848834). In that study, Keytruda — administered at 10 mg/kg every two weeks — had a 20 percent response rate in patients with advanced HNSCC whose tumors were positive for the protein PD-L1.

The findings reported May 29 were based on results from an expansion of that first trial, which involved 132 patients with advanced HNSCC who were recruited regardless of their PD-L1 or HPV status. Importantly, said Seiwert, patients in this cohort received a fixed dose of Keytruda (200 mg every three weeks), representing “a very convenient dosing schedule.”

Eligible patients had measureable disease based on RECIST 1.1 response evaluation criteria and an ECOG performance status of 0 or 1. The majority of enrollees were male (83 percent), and 56.8 percent had received two or more lines of therapy for disease recurrence. Radiographic imaging was used to assess tumor response every eight weeks. Patients were treated as long as they didn’t show progression of disease or as long as they demonstrated clinical improvement, Seiwert explained.

Of 117 evaluable patients, 29 (24.8 percent; [95 percent confidence interval (CI), 17.3–33.6]) responded to treatment with Keytruda. For patients with HPV-positive HNSCC, the ORR was 20.6 percent, and in the HPV-negative cohort, ORR was 27.2 percent.

“In addition to the 25 percent response rate,” said Seiwert, “about 25 percent also had stable disease, so when we take these together, we have a disease control rate of about 50 percent, which is remarkable in this disease, especially in a heavily pretreated population.”

Moreover, he said, about two-thirds of patients had received two or more prior lines of therapy, which generally is an indicator of a very poor prognosis.

For the 56 percent of patients whose tumors decreased in size, Seiwert said the responses often occurred early at eight or 16 weeks, although there were a few outliers with late responses.

“Importantly, those patients who did respond oftentimes continued to have responses — 86 percent of patients had durable responses in this cohort,” he continued, adding that not only are responders remaining on the therapy, but so are many patients who have stable disease, with a total of 40 patients staying on the drug.

“Overall, and in keeping with what we already know about pembrolizumab, this was a very well-tolerated agent,” said Seiwert, “certainly better tolerated than what we usually see in head and neck cancer with aggressive chemotherapy and radiotherapy.”

Serious side effects were reported in fewer than 10 percent of patients. The most common side effects were fatigue (15.2 percent of patients), hypothyroidism (9.1 percent), and decreased appetite and rash, each occurring in 7.6 percent of patients. Four patients discontinued treatment due to immune-related side effects: two due to grade 2 interstitial lung disease and grade 3 colitis, respectively, and two patients for grade 3 pneumonitis.

Analysis of the findings based on biomarker status is ongoing, and Seiwert is hopeful that with the emergence of new potential biomarkers, researchers will be able to pinpoint which patients with HNSCC are most likely to benefit from the immunotherapy.

For example, another related study that Seiwert and colleagues are reporting at ASCO (abstract 6017) has shown that the expression of the gene signature interferon-gamma in head and neck tumors had a very strong negative predictive value of response to Keytruda. “In the future, these results may help us, if validated, to determine which patients should or should not [be given] pembrolizumab,” Seiwert said.

Pembrolizumab versus standard treatment for HNSCC also is being evaluated in two phase 3 trials that are currently recruiting participants (NCT02252042 and NCT02358031).

Source:
Seiwert TY, Haddad RI, Gupta S, et al. Antitumor activity of the anti-PD-1 antibody pembrolizumab in biomarker-unselected patients with R/M head and neck cancer: preliminary results from the KEYNOTE-012 expansion cohort. J Clin Oncol. 2015;(suppl; abstr LBA6008) – See more at: http://www.curetoday.com/articles/keytruda-doubles-efficacy-of-only-targeted-therapy-for-head-and-neck-cancer/2#sthash.44VvpPH4.dpuf

Cure Possible for Some HPV-Positive Oropharyngeal Cancers

Source: www.medscape.com
Author: Fran Lowry

In a subset of patients with human papillomavirus (HPV)-related oropharyngeal cancer, the goal of achieving a “cure” is a realistic one, even in patients who have limited distant metastases, a prospective study has shown.

Of the patients with HPV-positive oropharyngeal cancer and distant metastases, 10% survived more than 2 years after intensive treatment, which the researchers defined as a cure.

The study was presented at the 5th International Conference on Innovative Approaches in Head and Neck Oncology (ICHNO) in Nice, France.

The research was praised by Jean Bourhis, MD, head of the Department of Radiation Oncology at Centre Hospitalier Université Vaudois in Lucerne, Switzerland, and cochair of the ICHNO conference scientific committee.

“This important piece of research adds substantially to what we know about the role and the importance of the human papillomavirus in oropharyngeal cancers and gives real hope of improvement in both diagnosis and treatment to those who are affected by the condition,” he said in a statement.

This study, from a world-leading group of head and neck cancer experts, is very interesting, and related to relevant clinical and interdisciplinary questions,” said Daniel Zips, MD, professor of radiation oncology at the University of Tübingen in Germany.

“HPV status is also important for the management of metastatic disease,” he told Medscape Medical News.

He agrees that for some patients with HPV-positive oropharyngeal cancer, using the researchers’ definition, a cure is possible.

“I also agree that the results from this study might begin to change the view of this disease and provide some hope for patients and their families,” Dr Zips explained.

Distant Metastases Are Main Form of Failure
“The majority of patients with HPV-related oropharyngeal cancer can be cured, but distant metastasis can occur in about 15% of patients. In fact, distant metastasis has become the main form of failure for this patient population,” lead author Sophie Huang, a radiation therapist and assistant professor at the University of Toronto. Dr Huang was a physician in China but is an MRT(T) — a radiation therapist — in Canada.

“When distant metastasis occurs, it is generally viewed as incurable disease. However, long-term survival after distant metastasis has been observed in nasopharyngeal cancer patients, which is another viral-related head and neck cancer, associated with the Epstein–Barr virus. Also, long-term survival in HPV-related OPC patients with distant metastasis has also been reported, but anecdotally,” Dr Huang told Medscape Medical News. “Are these just miracles? And would more miracles be found if we were able to understand how they happen?”

Dr Huang and her colleagues established a prospective database in which they collected data on enough patients to allow them to study how distant metastasis is manifested, how the cancer behaves after distant metastasis, and whether there are any factors that influence survival after distant metastasis.

“We felt that the answers to these questions would help us tailor surveillance strategies for the early detection of distant metastasis and explore optimal management algorithms to improve outcomes,” she explained.

Prospective Follow-up of Patients
The team evaluated 1238 consecutive oropharyngeal cancer patients treated at the Princess Margaret Cancer Centre in Toronto from 2000 to 2011. They identified 88 patients with HPV-related cancer and 54 with smoking-related cancer who were HPV-negative, all with distant metastases.

They assessed the pace of the manifestation of the distant metastases, characteristics, and patient survival, and identified factors that might predict longer survival.

The proportion of patients with distant metastases was similar in the two groups. However, metastases associated with HPV-positive oropharyngeal cancer had a later onset, different characteristics, and longer survival than those associated with HPV-negative oropharyngeal cancer.

Specifically, more than 94% of metastases occurred in the first 2 years after treatment in HPV-negative patients, whereas only a quarter occurred in HPV-positive cancers. In the HPV-positive group, some occurred after 5 years.

“This observation indicates that HPV-related OPC patients who are disease-free for 2 years are not out of the woods. A longer surveillance period for HPV-related OPC patients is needed to detect, and hopefully cure, distant metastases,” Dr Huang said.

Additionally, the researchers found two phenotypes of distant metastases in HPV-positive patients.

The disseminating phenotype is aggressive and spreads to multiple organs in a short period of time. This phenotype was found in 55% of the HPV-positive group but in 0% of the HPV-negative group.

The indolent phenotype is characterized by a few lesions growing at a slow pace, and manifesting as oligometastasis, with five or fewer lesions. In patients with metastases in a single organ, this phenotype was found in 24% of the HPV-positive group and in 26% of the HPV-negative group.

The lung was the most common site for distant metastasis in both groups.

“This indolent phenotype has longer survival and might be curable,” Dr Huang reported.

More HPV-positive than HPV-negative patients were specifically treated for distant metastasis (60% vs 31%)

table1

More HPV-positive patients with distant metastases than HPV-negative patients survived to 3 years (25% vs 15%; P = .01).

“The survival advantage in HPV-positive patients is due to a number of factors. The cancer is more sensitive to radiotherapy and chemotherapy, patients tend to be younger by about 10 years, and they have fewer other health problems, including those caused by smoking. This allows them to receive the more aggressive treatment necessary to eradicate metastatic disease,” Dr Huang explained.

table2

“This research shows that metastatic HPV-positive patients who receive active treatment can survive considerably longer. One of the reasons patients with metastatic disease fail to receive aggressive treatment is due to the physician and patient perception that this is an incurable state. We hope these results will motivate researchers to optimize management strategies for these patients,” Dr Huang said.

“The first distant metastasis site is mostly in the chest region,” she noted. In fact, most of the cured patients had lung metastasis. “Computed tomography of the thorax for the early detection of distant metastases” might enhance the cure rate for this disease, she added.

Future studies should look for ways to identify patients at initial presentation who are at high risk for distant metastasis, and which type of distant metastasis will develop.

“We know there is a degree of correlation between the initial stage and the risk of distant metastasis, but we did not find a strong relationship between this stage and the type of metastasis,” Dr Huang reported. “The intensity of cigarette smoking in the years prior to the time of diagnosis is a possible factor. Being able to identify such relationships could be a huge help in deciding appropriate treatment at an early stage.”

Note:

1. Dr Bourhis, Dr Zips, Dr Huang, have disclosed no relevant financial relationships.
2. 5th International Conference on Innovative Approaches in Head and Neck Oncology (ICHNO): Abstract OC-044. Presented February 13, 2015.

March, 2015|Oral Cancer News|