First UK clinical trial in proton beam therapy

Source: www.icr.ac.uk
Author: staff

Image: The Proton Beam Scanner. Credit: The Royal Christie NHS Foundation Trust

The first proton beam therapy clinical trial in the UK, co-led by The Institute of Cancer Research, London, is now taking place at The Christie NHS Foundation Trust in Manchester. The trial will determine whether the use of proton beam therapy reduces long-term side effects and improves quality of life for patients treated with radiotherapy for throat cancer.

The study, funded by Cancer Research UK with support from The Taylor Family Foundation started last year and, despite the Covid-19 pandemic, is recruiting ahead of target, with 37 patients so far taking part. In total 183 people will take part in the study, about two thirds will receive proton beam therapy, and a third will receive standard radiotherapy.

State of the art proton beam therapy
Currently all patients allocated proton treatment within the trial, which is called TORPEdO, receive this at the state of the art NHS proton beam therapy centre at The Christie in Manchester, which opened in 2018. Another centre is currently being built at University College London Hospitals.

A combination of chemotherapy and radiotherapy is usually effective in curing head and neck cancers, but radiotherapy can damage the healthy surrounding tissue. This can result in severe long-term side effects including dry mouth, loss of taste, difficulty chewing and swallowing and problems with hearing. Some patients might need to use a feeding tube for the rest of their lives.

Precisely target tumours
Proton beam therapy uses charged particles instead of X-rays and can target tumours more precisely, causing less damage to surrounding tissues.

A year after treatment, patients will be asked about their quality of life and doctors will assess the impact of any side-effects, and whether they still need to use a feeding tube a year after treatment, or have lost a significant amount of weight.

First proton beam therapy trial in the UK
Dr David Thomson, consultant clinical oncologist at The Christie and chief investigator on the trial, said:

“It’s very exciting and a privilege to conduct the first proton beam therapy trial in the UK here in Manchester. In what is a true team effort, the amount of support from colleagues across the country has been fantastic. There’s a real need to develop treatments which cause less side effects and improve long-term quality of life for patients with head and neck cancer. Proton beam therapy may do this, by reducing the damage to healthy surrounding tissues, so it was an obvious patient group to research first.

“Currently the proton beam therapy unit at The Christie is mainly used for children and young adults. We would like to make the facility available for other groups of adult patients who may benefit most from it too. The first step is to determine whether proton beam therapy improves side effects and quality of life for patients with throat cancer.”

Potentially transformative for patients
Professor Emma Hall, Deputy Director of the Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, who co-leads the study, said:

“Radiotherapy is a highly effective treatment involved in around 40 per cent of cancer cures, but it can cause side effects where radiation affects nearby tissues, and this can be a particular problem for patients with throat cancers. Proton beam therapy has the potential to target tumours more precisely, with less spillover of radiation into the neighbouring healthy tissue.

“We think that for patients with throat cancer, proton beam therapy could be transformative – minimising side effects, improving recovery and sparing some people the long-term impacts of treatment, such as the need to use a feeding tube. This trial is an important first step in understanding if proton beam therapy can deliver on its promise, and if so who stands to benefit most.”

The researchers will also study which patients benefit most from proton beam therapy to help them determine who to offer the treatment to in the future in terms of who is most likely to see long-term improvements.

Around 11,700 people are diagnosed with head and neck cancer every year in the UK, and more than 8 in 10 patients suffering from throat cancer – such as tonsil and base of tongue cancer – receive radiotherapy as part of their treatment.

‘An incredible achievement’
Michelle Mitchell, chief executive of Cancer Research UK, said:

“It’s fantastic to hear that despite the challenges that this pandemic has thrown at us, patients with head and neck cancer have been able to access cutting-edge treatments like proton beam therapy. Many patients used to have to travel abroad to receive this type of treatment, so to be pioneering its use for adults in the UK is an incredible achievement.

“Cancer Research UK has a solid history of delivering practice-changing radiotherapy trials, which included making IMRT the gold standard for treating head and neck cancers. But there is always room for improvement, and we hope that proton beam therapy will be the next step in transforming the lives of people with neck and head cancer.”

Neville Shepherd from The Taylor Family Foundation said:

“We are delighted to see the trial proceed against the headwinds of Covid-19. It’s wonderful to know a cohort of 24 patients are already receiving proton beam therapy treatment for their throat cancer. We thank all involved for dealing with the challenges of set up and delivery of the trial in these extraordinary times.”

Addenbrooke’s to use Microsoft’s AI tool to speed up cancer treatment

Source: www.governmentcomputing.com
Author: staff

Microsoft said that Addenbrooke’s Hospital in Cambridge, UK, will use its artificial intelligence (AI) technology powered InnerEye tool for speeding up cancer treatment.

Developed at its Cambridge Research Lab, the InnerEye project helps in developing AI models that leverage the hospital’s own data to automatically show tumours and healthy organs on patient scans. These are then checked and confirmed by a clinical oncologist prior to giving treatment to the patient, said Microsoft.

According to the tech major, the process will reduce the otherwise lengthy treatment planning stage, which is crucial for head and neck cancers, which can multiply quickly if left untreated. Microsoft claims that InnerEye can help execute contouring process in complex cases 13 times faster than the current approach.

Addenbrooke’s Hospital oncologist and InnerEye co-lead Dr Raj Jena said: “The results from InnerEye are a game-changer. To be diagnosed with a tumour of any kind is an incredibly traumatic experience for patients.

“So as clinicians we want to start radiotherapy promptly to improve survival rates and reduce anxiety. Using machine learning tools can save time for busy clinicians and help get our patients into treatment as quickly as possible.”

Run by Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s is a teaching hospital, research centre, and also a designated academic health science centre.

Addenbrooke’s Hospital and Microsoft are said to have been collaborating over the last eight years to develop and pilot InnerEye. The hospital will become the first NHS facility to have introduced a deep-learning solution trained on its own data, once the AI tool is deployed.

Microsoft said that to make sure that all hospitals can use the InnerEye Deep Learning Toolkit, the company has made it available freely as opensource software. However, clinical use of machine learning models is subject to approval from relevant regulators.

Microsoft Research Cambridge principal research manager Javier Alvarez-Valle said: “AI models trained with InnerEye are changing the way cancer is treated, speeding up the process to give patients greater peace of mind and empowering clinical oncologists with an AI assistant.

“The AI works in the background, so clinical oncologists just open up the scans on their computer and they can see what their AI model has highlighted. The clinical oncologist then decides what to do with that information.

“AI models trained with InnerEye will be hosted in Microsoft’s Azure cloud, so all the data is securely held in the UK and only available to the medical staff who need to use it.”

2020-12-12T10:01:59-07:00December, 2020|Oral Cancer News|

Deep learning models for image-guided RT in head and neck and prostate cancers

Source: www.journalofclinicalpathways.com
Author: Lisa Kuhns

Machine learning models achieve clinically acceptable accuracy in image segmentation tasks in radiotherapy planning and reduce overall contouring time for head and neck and prostate cancers, according to a recent study in JAMA Network Open (2020;3[11]:e2027426. doi:10.1001/jamanetworkopen.2020.27426)

Personalized radiotherapy planning requires large time commitments for oncologists and processes often vary among experts and institutions.

Authors aimed to explore clinically acceptable autocontouring solutions that can be integrated into clinical practice and used in different radiotherapy areas.

Researchers evaluated multicenter imaging data set made up of 519 pelvic and 242 head and neck computer tomography scans from 8 clinical sites. Patients in the study were diagnosed with either prostate or head and neck cancer. The models were trained to automatically delineate organs at risk and evaluated internal and external datasets. Models were compared against expert annotations in an interobserver variability (IOV) study.

For 13 of the 15 structures, the models performed within the bounds of expert IOV. For internal vs external data sets, the models achieved mean [SD] Dice scores for left femur at 98.52% and 98.04% (P = .04), respectively.

“In this study, the models achieved levels of clinical accuracy within expert IOV while reducing manual contouring time and performing consistently well across previously unseen heterogeneous data sets,” concluded the study authors. “With the availability of open-source libraries and reliable performance, this creates significant opportunities for the transformation of radiation treatment planning.”—Lisa Kuhns

2020-12-11T09:20:35-07:00December, 2020|Oral Cancer News|

Experts release new guidelines for studies into most effective treatments for HPV-positive throat cancer

Source: en.brinkwire.com
Author: provided by University of Birmingham, United Kingdom

Heightened caution is needed when considering de-escalation trials for patients with Human papillomavirus (HPV)-positive oropharyngeal cancer (OPC), to ensure minimal harm to patients, new guidelines from a group of international head and neck cancer experts have suggested.

HPV-positive oropharyngeal cancer is a cancer of the throat caused by the human papillomavirus—a common, but symptomless group of sexually transmitted viruses. Instances of many throat and neck cancers have declined as smoking rates have fallen, whereas HPV-positive OPC has increased, largely affecting younger patients.

The standard course of treatment for this disease is a combination of cisplatin (a common chemotherapy drug) and radiotherapy. The younger age of the patient population, significantly improved prognosis, and relatively minimal morbidities caused by the standard treatment pathway have led to the popularisation of the concept of treatment de-escalation as a way to improve the quality of life of patients by reducing dosage or frequency of treatment.

These new recommendations, published today in the Journal of Clinical Oncology have been created by the Head and Neck Cancer International Group, a group of experts from nineteen countries, led by the University of Birmingham, UK. The guidelines have been prompted by the recent results of the first three randomised de-escalation trials which suggested a clear detriment in survival when cisplatin is omitted or substituted to minimise side effects.

After a review of available HPV-positive OPC literature, the guidelines recommend an overall need for caution when considering de-escalation options, even in instances where there appears to be possible favourable disease outcomes. Experts also recommend a revised approach to how findings are evaluated during phase II studies to ensure that any potential risks to survival are identified and only if none are present should phase III trials follow.

The guidelines also recommend that de-escalation trials should only be considered for well-defined, very low risk groups and only when there is a strong rationale for investigating a particular treatment strategy. Additionally harm-minimisation techniques should be considered as an alternative. Importantly, treatments should not be implemented into clinical practice before high level evidence is available.

Corresponding author Professor Hisham Mehanna, Director, Institute of Head and Neck Studies and Education (InHANSE) at the University of Birmingham said: “Clinicians and researchers have to be careful when planning and undertaking de-escalation studies, as trials to date have that harm can befall patient. Very controlled and small strides need to be taken when evaluating a possible de-escalation strategy, especially one that removes cisplatin.”

A new tool to predict delays in post-surgical radiotherapy for head and neck cancer

Source: www.eurekalert.org
Author: Medical University of South Carolina news release

More than 65,000 Americans are diagnosed annually with head and neck cancer, which most often occurs inside the mouth and throat. For patients who undergo surgery to treat this cancer, guidelines recommend that prompt initiation of radiotherapy — within six weeks — is critical for best outcomes.

Unfortunately, delays in initiating post-operative radiotherapy (PORT) are far too common. Patients do not always understand the importance of prompt initiation of radiotherapy and may have to overcome other barriers, such as lack of social support and insurance. In addition, health care providers do not always communicate with one another or coordinate care. These avoidable delays have a negative impact on outcomes in a disease that claims almost 15,000 lives in the U.S. each year.

To ameliorate this crisis, a research team at the Medical University of South Carolina has developed and validated tools known as nomograms to help predict treatment delays in high-risk patients based on individualized risk factors. The team was led by Evan Graboyes, M.D., an assistant professor in the Department of Otolaryngology-Head & Neck Surgery at MUSC and a member of the Cancer Control Program at Hollings Cancer Center. The results of the nomogram study were reported in JAMA Otolaryngology-Head & Neck Surgery.

“A nomogram is a graphical representation of a mathematical model that we are using to predict how likely it is that a patient with head and neck cancer may have a treatment delay,” explained Graboyes. “We hope that these nomograms can be used to identify patients at highest risk for treatment delays so that we can target interventions to them to decrease the risk of delay.”

Standard-of-care treatment for patients with head and neck cancer combines surgery, radiation and chemotherapy. However, treatment outcomes remain very poor, and only about 50% of head and neck cancer patients with advanced disease will survive after 5 years.

With the goal of improving the survival rate of patients with head and neck cancer, Graboyes and his team developed and validated two types of nomograms for predicting delays in PORT. The study examined pre- and post-surgical data from 60,766 adult patients with head and neck cancer, grouped into different cohorts.

The first nomogram is based on information available to both the clinician and patient during the surgical consultation. At this point, the patient will know whether he or she is likely going to have surgery followed by radiation therapy. “This type of nomogram will provide a personalized estimate of the risk of delay commencing PORT and can be used to enhance counseling and guide interventions for patients with higher risks of delay,” explained Graboyes.

The findings of Graboyes’ study suggest that stage 4 cancer and oral cavity sites are two of the main variables associated with delayed PORT initiation. Knowing this type of information beforehand will enable patients to obtain pre-surgical dental oncologic treatment referrals and may greatly improve timely PORT introduction.

The second nomogram incorporates information from before and after surgery. According to Graboyes, this nomogram can be used by health care systems to compare their rates of PORT delay in a risk-adjusted fashion that acknowledges differences in the types of patients being treated.

In addition, the nomogram may guide quality improvement initiatives. For example, one of the key factors associated with delayed PORT was prolonged length of stay after surgery. This information may help physicians to reduce the length of time patients stay in the hospital after surgery, eliminating one hurdle to prompt initiation of radiation treatment.

Although the two nomograms were developed in one cohort of patients and validated in a second cohort of patients with head and neck cancer from across the U.S., the study still had some key limitations. The nomogram didn’t account for individual patient education, income, social support, dental disease, smoking or alcohol consumption. Therefore, more research will be needed to understand the degree to which these factors lead to delays in PORT initiation. A future study will help to address some of these limitations.

Graboyes believes that the current study will help head and neck cancer patients get the treatment they need and improve their chance of survival.

“I would love it if patients and clinicians would be able to use the nomogram website to get more precise, quantitative information about the risk of PORT delay and use it to educate patients, counsel them before treatment and communicate risk precisely,” said Graboyes. “We know that getting patients timely head and neck cancer care that follows guidelines is a promising strategy to improve survival among these patients. I hope these nomograms will be a practical and useful tool as we work toward the goal of decreasing treatment delays.”

Insurance coverage key to timely care in head and neck cancer cases

Source: www.eurekalert.org
Author: Medical University of South Carolina

A study published in the JAMA Otolaryngology-Head & Neck Surgery examines the effect of Medicaid expansion on head and neck cancer patients, finding that the expansions under the Affordable Care Act (ACA) were associated with improved access to care for these patients and selective Medicaid expansion may worsen existing regional disparities in terms of access to care and outcomes.

Medicaid expansion refers to a provision in the ACA that called for expansion of Medicaid eligibility to cover more low-income Americans. It was determined that each state would decide whether to participate in the expansion – accept federal funds – or not. As of 2020, 37 states including the District of Columbia accepted Medicaid expansion. South Carolina is one of 14 states that has not. As a result, there are gaps in coverage for adults who have incomes above Medicaid eligibility limits yet still below the poverty level, exacerbating challenges with access to care, which is vital in the early detection of cancer.

“We performed the study because delivering timely head and neck cancer care is critical for optimal outcomes,” said Evan Graboyes, M.D., a researcher at Hollings Cancer Center at the Medical University of South Carolina and senior author on the study. The surgeon at MUSC Health specializes in the treatment of head and neck cancers.

The team analyzed data from a national sample of nearly 91,000 adults with newly diagnosed head and neck cancer who were identified from the National Cancer Database. In this observational study, researchers examined the effect that Medicaid expansion, as part of the ACA, had on the patients’ stages of cancer at the time of diagnosis as well as treatment delays for these patients.

Medicaid expansions are known to increase the percentage of patients getting treatment who have localized (stages I or II) cancer at diagnosis for cancers such as colon and breast cancer that have screening tests. Graboyes said the researchers wanted to know the effect of Medicaid expansions on head and neck cancer, which lacks a screening test, he said.

The study showed in states that expanded Medicaid as part of the ACA, patients with head and neck cancer were more likely to be diagnosed with localized (stages I to II) cancer and initiate treatment in a timelier fashion than patients in nonexpansion states. Because of the strong association with a particular stage at diagnosis and the timely treatment that leads to survival for head and neck cancer, the study suggests that Medicaid expansion that offers insurance coverage may help to improve outcomes for these patients.

“I hope that the data we produce gets referenced and is used by policy makers in the future,” Graboyes said.

Helmneh Sineshaw, M.D., lead author on the study and a principal scientist at the American Cancer Society, said the study found that Medicaid expansion provided a huge benefit to those who didn’t have access to insurance, leading to earlier diagnosis and timely treatment.

“What we find is that patients, in states that expanded Medicaid, had a greater chance of being diagnosed early, whereas patients living in nonexpansion states were likely to be diagnosed in a more advanced stage,” Sineshaw said.

Graboyes said delays in the delivery of head and neck cancers are a key driver of suboptimal survival for patients with head and neck cancers and contribute to racial disparities in mortality. Head and neck cancers are rising in number and carry a high mortality rate, with black patients even more likely to die from it.

This study adds to a growing portfolio of other health disparity studies by Graboyes and colleagues, including:

A 5-year $1.2 million grant from the National Cancer Institute awarded in 2019 to decrease mortality and racial disparities in survival for head and neck cancer patients by developing innovative interventions to improve the timeliness, equity and quality of care delivery.

A 2018 study in JAMA Otolaryngology-Head & Neck Surgery that found that ensuring head and neck cancer patients receive postoperative radiotherapy within six weeks of their surgical procedure maximizes their chances of a cure.

Graboyes said more research is needed to understand more fully how changes in insurance coverage affects patients with head and neck cancer. Although there is a strong relationship between the patient’s stage at diagnosis and timely treatment, the current study does not address whether Medicaid expansion is associated with fewer recurrences or better survival since there has not been enough time since the implementation of Medicaid expansion to answer this question.

Another limitation of the current study is that it did not analyze how Medicaid expansion was associated with changes in the cost of treatment for head and neck cancer patients. More research is needed to understand the relative costs of expansion of Medicaid provisions as compared to the assumed cost savings of catching and treating head and neck cancers in a more localized stage (I to II) versus advanced stages (III to IV), he said.

“The study is an important first step in understanding how insurance coverage affects health care delivery for patients with head and neck cancer, particularly those who, due to lack of insurance coverage, are more likely to present with advanced disease and experience treatment delays.”

Fewer side effects with proton beam vs traditional radiotherapy

Source: www.medscape.com
Author: Roxanne Nelson, RN, BSN

One of the main advantages claimed for proton beam radiotherapy is that it has fewer adverse effects than traditional radiotherapy. A new study suggests that that is so. The retrospective comparative effectiveness study involved 1483 patients with nonmetastatic cancer (various types, including brain, head and neck, lung, gastrointestinal, gynecologic) who were treated with curative intent. Slightly less than a third of these patients (n = 391) were treated with proton beam radiotherapy; the remaining patients (n = 1092) underwent traditional radiotherapy.

The results show that among the patients who were treated with proton therapy, there was a significantly lower risk for serious side effects: 11.5% experienced events of grade 3 or higher within 90 days of treatment, compared to 27.6% of patients in the traditional radiotherapy group.

“We know from our clinical experience that proton therapy can have this benefit, but even we did not expect the effect to be this sizeable,” said senior author James Metz, MD, chair of radiation oncology, leader of the Roberts Proton Therapy Center at the University of Pennsylvania, and a member of Penn’s Abramson Cancer Center.

Importantly, there was no difference in cancer outcomes between the two groups; both disease-free and overall survival were similar.

“It shows that proton therapy offers a way for us to reduce the serious side effects of chemoradiation and improve patient health and well-being without sacrificing the effectiveness of the therapy,” said lead author Brian Baumann, MD. He is an adjunct assistant professor of radiation oncology at Penn and an assistant professor of radiation oncology at the Washington University School of Medicine in St. Louis.

The study was published online December 26 in JAMA Oncology.

It provides a “compelling hypothesis that patients undergoing chemoradiotherapy for locally advanced cancer may benefit from the use of proton therapy, potentially leading to major cost savings for patients, payers, and society at large,” comment the authors of an accompanying editorial. The authors are Henry S. Park, MD, MPH, and James B. Yu, MD, MHS, both from Yale University School of Medicine, New Haven, Connecticut.

Need for Randomized Clinical Trials
The results from this study were initially presented at the 2019 annual meeting of the American Society of Clinical Oncology and were reported by Medscape Medical News at that time.

At the meeting, Baumann commented that, if the side effects are reduced, then it may be possible to intensify therapy, which in turn could improve survival.

But the “real take-home message here is that the 90-day toxicity is lower,” he said. “Grade 3 and higher toxicity usually requires hospitalization. It means a trip to the ER [emergency room], getting admitted, and a possibly worse outcome.”

Baumann emphasized that an important next step is to conduct randomized clinical trials of proton therapy vs proton chemoradiotherapy. “Efforts are already underway to do these studies for some cancers,” he said. “I think it’s important that we support these trials and encourage accrual on these trials.”

Psychological impact of head and neck cancers

Source: pharmafield.co.uk
Author: Emma Morriss

Bristol-Myers Squibb (BMS), in partnership with patient groups The Swallows and the Mouth Cancer Foundation, have announced the results from a patient survey into the psychological impact of head and neck cancers. The research explored the long-term burden of treatment on head and neck cancer patients.

After undergoing treatment for head and neck cancer, which can include surgery, chemotherapy or radiotherapy, many patients report an ongoing impact on their day-to-day life. However, 55% of the 118 patients surveyed indicated they did not receive the right level of information in preparation for the complications encountered from treatment.

There are around 11,900 new head and neck cancer cases in the UK every year and the incidence of head and neck cancer has increased by 32% since the early 1990s.

Following treatment, the survey showed 56% of patients had problems with simple things like swallowing, often experiencing severe pain, while two-thirds of patients experienced changes in their voice or speech. The survey also showed self-reported change from pre- to post- treatment in vital areas including a drop in the ability to communicate (37%), memory loss (21%), and trouble sleeping (20%).

As well as physical symptoms, treatment can have severe implications on mental health too. 52% of patients reported feelings of anxiety before treatment, which only reduced to 48% following treatment. However, emotional and psychological support was only offered to 46% of patients.

A majority of patients did receive access to a clinical nurse specialist, however there was still 23% who were not offered this service. Clinical nurse specialists use their skills and expertise in cancer care to provide physical and emotional support, coordinate care services and inform and advise patients on clinical as well as practical issues, which have been shown to lead to more positive patient outcomes.

“These results show the impact treatment may have on head and neck cancer patients. The continued problems and symptoms experienced by patients after treatment significantly impacts patients’ daily life. We also know physical disfigurement can increase social anxiety. It is important that we raise the awareness of this and work together to provide solutions to improve and support patient outcomes.” said Mouth Cancer Foundation, Clinical Ambassador, Mr Mahesh Kumar.

“With the incidence of head and neck cancers increasing, it is vital we understand what we can do to help patients. We are so pleased to have worked in collaboration with BMS and the Mouth Cancer Foundation to help raise awareness of this disease and understand where patients might need more help to reduce the impact on their lives. We know head and neck cancers, and the associated complications, do not get a lot of attention so it’s crucial for awareness days such as World Head and Neck Cancer Day to be used to shine a light on the disease. By doing so, it will help to improve detection, treatment and outcomes for patients.” commented Chris Curtis, Chairman of The Swallows.

Standard chemotherapy treatment for HPV-positive throat cancer remains the most effective, study finds

Source: www.eurekalert.org
Author: press release, University of Birmingham

A new study funded by Cancer Research UK and led by the University of Birmingham has found that the standard chemotherapy used to treat a specific type of throat cancer remains the most effective.

The findings of the trial, which aimed to compare for the first time the outcomes of using two different kinds of treatment for patients with Human papillomavirus (HPV)-positive throat cancer, are published today (November 15th) in The Lancet.

Throat cancer is one of the fastest rising cancers in Western countries. In the UK, incidence was unchanged between 1970 and 1995, then doubled between 1996 and 2006, and doubled again between 2006 and 2010. The rise has been attributed to HPV, which is often a sexually transmitted infection. Most throat cancers were previously caused by smoking and alcohol and affected 65 to 70 year old working class men. Today, HPV is the main cause of throat cancer and patients are middle class, working, have young children and are aged around 55.

HPV-positive throat cancer responds well to a combination of cisplatin chemotherapy and radiotherapy, and patients can survive for 30 to 40 years, but the treatment causes lifelong side effects including dry mouth, difficulty swallowing, and loss of taste.

The De-ESCALaTE HPV study, which was sponsored by the University of Warwick, compared the side effects and survival of 164 patients who were treated with radiotherapy and cisplatin, and 162 who were given radiotherapy and cetuximab. The patients were enrolled between 2012 and 2016 at 32 centres in the UK, Ireland, and the Netherlands. Patients were randomly allocated to be treated with radiotherapy and either cisplatin or cetuximab. Eight in ten patients were male and the average age was 57 years.

Importantly, the results found that there was very little difference between the two drugs in terms of toxicity in patients and side effects such as dry mouth, however, there was a significant difference in the survival rates and recurrences of cancer in patients taking part in the trial.

They found that the patients who received the current standard chemotherapy cisplatin had a significantly higher two-year overall survival rate (97.5%) than those on cetuximab (89.4%). During the six-year study, there were 29 recurrences and 20 deaths with cetuximab, compared to 10 recurrences of cancer and six deaths in patients who were treated with the current standard chemotherapy cisplatin.

And cancer was three times more likely to recur in two years following treatment with cetuximab compared to cisplatin, with recurrence rates of 16.1 per cent versus six per cent, respectively.

Study lead Professor Hisham Mehanna, Director of the University of Birmingham’s Institute of Head and Neck Studies and Education, said: “Many patients have been receiving cetuximab with radiotherapy on the assumption that it was as effective as cisplatin chemotherapy with radiotherapy and caused fewer side effects but there has been no head-to-head comparison of the two treatments.

“Cetuximab did not cause less toxicity and resulted in worse overall survival and more cancer recurrence than cisplatin.

“This was a surprise – we thought it would lead to the same survival rates but better toxicity. Patients with throat cancer who are HPV positive should be given cisplatin, and not cetuximab, where possible.”

Dr Emma King, Cancer Research UK Associate Professor in head and neck surgery at the University of Southampton, said: “Studies like this are essential for us to optimise treatments for patients. We now know that for HPV-positive throat cancer, the standard chemotherapy treatment remains the most effective option.

“However, we must keep testing new alternatives to ensure patients always have access to cutting-edge and kinder treatments. Chemotherapy and radiotherapy can leave head and neck cancer patients with long term pain and difficulties swallowing, so we should always strive to minimise side effects.”

Professor Janet Dunn from the University of Warwick, whose team ran the De-ESCALaTE HPV trial, said: “In the current trend for de-escalation of treatment, the results of the De-ESCALaTE HPV trial are very important as they were not as we expected. They do highlight the need for academic clinical trials and are an acknowledgement of the key role played by Warwick Clinical Trials Unit at the University of Warwick as the co-ordination and analysis centre for this important international trial.”

The patients on the De-ESCALaTE trial Steering Committee endorsed the importance of research findings.

Malcom Babb, who is also President of the National Association of Laryngectomee Clubs, said: “From a patient perspective, De-ESCALaTE has been a success by providing definitive information about the comparative effectiveness of treatment choices.”

2018-11-16T09:36:03-07:00November, 2018|Oral Cancer News|

No De-escalation of Therapy for HPV+ Throat Cancer

Source: www.medscape.com
Author: Alexander M. Castellino, PhD

Another trial has shown that de-escalating therapy does not work in patients with good prognosis human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma or throat cancers.

Results from the De-ESCALaTE HPV study show that using the targeted drug cetuximab with radiotherapy does not improve side effects and, more importantly, has worse survival compared with the standard of care — chemotherapy with cisplatin and radiotherapy.

The finding echoes the results from the US National Cancer Institute’s Radiation Therapy Oncology Group (RTOG) 1016 trial, the top-line results of which were released earlier this year, and details of which were presented this week at the American Society of Radiation Oncology (ASTRO) 2018 meeting.

“Do not change your clinical practice of using cisplatin with radiotherapy in these patients,” cautioned Hisham Mehanna, MBChB, PhD, chair of head and neck surgery at the University of Birmingham, United Kingdom, and lead investigator of the De-ESCALaTe study. He presented the results during a presidential session here at the European Society for Medical Oncology (ESMO) 2018 Congress (abstract LBA9).

“Cetuximab did not cause less toxicity and resulted in worse overall survival and more cancer recurrence than cisplatin. This was a surprise — we thought it would lead to the same survival rates but better toxicity. Patients with throat cancer who are HPV+ should be given cisplatin, and not cetuximab, where possible,” Mehanna said in a statement.

Hope for Fewer Side Effects
Cetuximab with radiation is already approved by the US Food and Drug Administration for use in head and neck cancer, including oropharyngeal cancer, and is an accepted standard of care, especially for patients who cannot tolerate cisplatin.

The hope behind de-escalation of therapy was that this regimen would offer similar efficacy but have fewer side effects than the standard regimen of cisplatin plus radiation.

“The side effects of treatment for patients with head and neck cancers are devastating. They experience loss of speech, loss of taste, and have trouble swallowing,” explained ESMO expert Jean-Pascal Machiels, MD, PhD, head of the department of medical oncology at the Cliniques Universitaires Saint-Luc, Brussels, Belgium.

“With HPV increasing rapidly in the Western world, HPV+ head and neck cancers are typically seen in younger patients who respond well to treatment and live for three to four decades. These patients would like to live without the toxicities associated with treatment,” he added.

“Based on a large study in 2006, many patients have been receiving cetuximab with radiotherapy on the assumption that it was as effective as chemotherapy with radiotherapy and caused fewer side effects,” Mehanna commented. That study showed that for patients with squamous cell carcinoma of the head and neck, treatment with cetuximab and high-dose radiotherapy improved locoregional control and reduced mortality. At the same time, side effects were no worse (N Engl J Med. 2006;354:567-578).

 

OCF NOTE: The foundation’s donors were funders of the RTOG 1016 clinical trial over several years.

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