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.

Patients with HPV-positive oropharynx cancer should receive chemoradiation

Source: medicalxpress.com
Author: provided by European Society for Medical Oncology

Patients with human papilloma virus (HPV)-positive throat cancer should receive chemoradiotherapy rather than cetuximab with radiotherapy, according to late-breaking research reported at the ESMO 2018 Congress in Munich.

“Many patients have been receiving cetuximab with radiotherapy on the assumption that it was as effective as chemotherapy with radiotherapy and caused less side effects but there has been no head-to-head comparison of the two treatments,” said study author Prof Hisham Mehanna, Chair, Head and Neck Surgery, Institute of Cancer and Genomic Sciences, University of Birmingham, UK.

Throat cancer is rapidly becoming more common in Western countries. For example in the UK, incidence was unchanged in 1970 to 1995, then doubled in 1996 to 2006, and doubled again in 2006 to 2010.The rise has been attributed to HPV, a sexually transmitted infection. Most throat cancer was previously caused by smoking and alcohol and affected 65-70 year-old working class men. Today HPV is the main cause and patients are around 55, middle class, working, and have young children.

HPV-positive throat cancer responds well to a combination of cisplatin chemotherapy and radiotherapy, and patients can survive for 30-40 years, but the treatment causes lifelong side effects including dry mouth, difficulty swallowing, and loss of taste. Patients deemed unable to tolerate chemotherapy, for example because of poor kidney function or older age, receive cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, and radiotherapy.

This study compared side effects and survival with the two treatments in 334 patients with HPV-positive throat cancer enrolled from 32 centres in the UK, Ireland, and the Netherlands. Patients were randomly allocated to radiotherapy and either cisplatin or cetuximab. Eight in ten patients were male and the average age was 57 years.

During the two-year study there were ten recurrences and six deaths with cisplatin compared to 29 recurrences and 20 deaths with cetuximab. Patients on cisplatin had a significantly higher two-year overall survival rate (97.5%) than those on cetuximab (89.4%; p=0.001, hazard ratio [HR] 4.99, 95% confidence interval [CI] 1.70-14.67). Cancer was over three times more likely to recur in two years with cetuximab compared to cisplatin, with recurrence rates of 16.1% versus 6.0%, respectively (p=0.0007, HR 3.39, 95% CI 1.61-7.19).

There were no differences between groups in the overall number of side effects, or of acute or late severe (grade 3-5) toxic events including dry mouth and difficulty swallowing. There were significantly more serious adverse events such as renal and haematological problems with cisplatin than with cetuximab.

Mehanna said: “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.”

Commenting on the study for ESMO, Dr. Branislav Bystricky, Head, Medical and Radiation Oncology Department, University Hospital Trencin, Slovakia, said: “It was believed that cetuximab causes less side effects and was therefore a good option for HPV-positive throat cancer patients who are young and expected to survive for several decades, as well as those less able to tolerate chemotherapy. This study shows that the best treatment choice for patients with HPV-positive throat cancer is cisplatin and radiotherapy. This combination gives ‘double’ the benefit since it is more effective in terms of survival and does not worsen all grade toxicity compared to cetuximab with radiotherapy.”

Bystricky noted that the results were in agreement with interim findings of the US National Cancer Institute’s RTOG 1016 trial, which is scheduled to report this month. He said: “We now have two studies showing that these patients should not be given cetuximab. Future research should examine whether genotyping for the KRAS-variant can select a group of patients that will benefit from cetuximab treatment with radiotherapy.”

Long-term implant failure in patients treated for oral cancer by external radiotherapy: a retrospective monocentric study

Source: Journal of Oral Medicine and oral Surgery, JOMOS
Date: October 10th, 2018
Authors: Aline Desoutter, Sophie Deneuve, Sophie-Charlotte Condamin and Anne-Gaëlle Chaux-Bodard

Abstract

Introduction: The placement of dental implants in irradiated bone has allowed functional rehabilitation for many oral cancer patients. Nonetheless, there is only few data about implant failure in irradiated tissues and their consequences. This retrospective study aims to highlight the rate and circumstances of implant failure.

Material and method: Patients treated with external radiotherapy for oral carcinoma and who received dental implants were included. Patients reconstructed with free bone flaps were excluded.

Results: Eighteen patients were included. Forty implants were placed between 2004 and 2007, 8 failed, of whom one osteoradionecrosis was observed. Time interval between radiotherapy and implantation was 44.6 (6–182) months. Mean dose was 51.8 (50–66) Gy.

Discussion: In the series, the implant failure rate is 20%, which corroborates the literature’s data. Failures occur more often for doses over 50 Gy. The placement of dental implant in irradiated bone leads to soft tissue complications but also increases the risk of osteoradionecrosis. The recent reimbursement of dental implants in oral cancer patients by the National Social Health system will probably increase the indications. Multidisciplinary staffs should be aware of benefit/risk ratio for each patient.

Introduction

Dental implants in patients treated for upper aerodigestive tract (UADT) cancers have facilitated the functional and aesthetic rehabilitation of patients whose postoperative anatomy did not allow for the placement of conventional prostheses. Several studies have been conducted and the success rates have varied from 62.5% to over 90% [1]. These success rates would be similar to those found in a healthy patient’s mandible, which is reported to be 92.6% [2]. However, there is little information regarding the types of failures that occur with these implants, as well as the consequences and circumstances surrounding their occurrence, especially when the radiation dose at the implant site is >40 Gy. Indeed, most of the published studies are case studies in which there is great heterogeneity in the initial tumor sites and in the radiation doses received at the implant site. It is therefore difficult to precisely determine the failure risk in patients who have received large radiation doses in the oral area. The expected complications are mainly peri-implantitis, loss of implants, and even osteoradionecrosis (ORN) [3]. The aim of this study was to highlight long-term implant failures in patients who were treated with radiotherapy for oral cancer and to observe the circumstances and consequences of these failures.

Material and methods

The clinical records of oral cancer patients treated between 2004 and 2007 by radiotherapy (exclusively or not) and who received implants were reviewed. In the interest of maintaining the homogeneity of the study sample, patients treated with a microanastomosis fibula flap were excluded.

The following information was extracted from the case records: tumor location, tumor stage, and type of treatment received, the duration between radiotherapy and implantation, the type of implants placed, the surgical and operative protocol, the patient’s medical history (excluding oncology) as well as any implant or peri-implant clinical events and their time of occurrence. Failure was defined as loss of implant osseointegration resulting in implant loss or removal. Surgical and implant loading failures were considered. Statistical analysis was performed using XLSTAT® software (Microsoft).

Results

Eighteen patients, consisting of 14 males (77%) and four females (13%) were eventually included. The mean age at the time of implant placement was 57.5 years (range: 42–78 years).

The initial tumor locations, the initial tumor stage, and the treatments received are presented in Table I.

Table I : Population studied: sites, tumor stages, and treatments received.
Table II : Implant failures as a function of the radiation dose received, initial tumor site, and failure onset delay.

Discussion

Cervicofacial radiation is one of the primary causes of implant loss [1,4] regardless of whether it is administered early or late [5]. Several failure factors specific to implant placement in irradiated areas have been identified; these include the duration after radiotherapy and the radiation dose received.

For successful implantation, the minimum time after radiotherapy before implantation should be 6–12 months [6]. A delay of >12 months would improve implant success rates [7]. In the current study, a minimum period of 6 months was selected after the multidisciplinary consultation with the surgical oncologists and radiotherapists. After excluding the two patients who were treated several years ago, missed their follow-up, and then reappeared for prosthetic rehabilitation, the average implantation time after radiotherapy in our study was 20.37 months (range: 6–49 months). One study [8] showed that the failures are less severe in patients receiving implants a later stage of oncological treatment (17.1% failure rate for intraoperative implants versus 4.6% for those placed postoperatively). Of course, the idea of early rehabilitation encourages the surgical team to perform implantation along with tumor removal, before additional treatments are administered. Although this technique has the advantage of decreasing treatment duration, it is not always feasible because of the constraints of tumor management.

The radiation dose received at the implant site is also a major cause of implant failure, with doses <50 Gy being more favorable [9,10]. Animal studies and literature reviews show that the implant failure rate is directly correlated with the radiation dose received [9,10]. In the study, implant sites that received estimated doses >55 Gy had failure (mean: 59.33 Gy). In fact, all implant failures occurred in patients who received treatment for cancer involving the anterior aspect of the floor of the mouth. The therapeutic target was therefore very close to the implant site, and the dose administered at the implant site was close to the therapeutic dose delivered.

The biggest challenge consists in evaluating the radiation dose received at the implantation site. In most studies, the initial tumor sites involved all the UADTs, including the oropharynx, with low radiation doses of about 30 Gy at the symphyseal and parasymphyseal level. It therefore seems more appropriate to limit the evaluation of failure rates to patients treated for cancer of the oral cavity, as the radiation doses at the implant site are therefore more homogeneous. In published studies, only a few authors [11] highlight the antecedents or lack thereof of radiation, with irradiated tissue implants having osseointegration rates of 83% at 5 years.

Long-term implant survival rates reported by the previous clinical studies are nonhomogeneous, with values of 72.8% at 10 years [9], 24% at 5 years [10], or 72% at 8 years [11]; however, these values support the results of our present study. Thus, Wagner [12] reports a 5-year osseointegration rate of 97.5% and at 10 years of 72.8%, whereas other authors report success rates of 48.3% [3]. Another study reports complications in 41.5% patients [13].

Seven out of eight failures encountered in the series began with peri-implantitis. Werkmeister [14] observed a soft-tissue complication rate of 28.6% in irradiated areas versus 8.3% in nonirradiated areas. These complications can be explained in part by the small amount of keratinized gingiva, along with the predisposing factors of radiotherapy-related sensitization and dry mouth. The occurrence of peri-implantitis should be carefully monitored to avoid ORN [15].

An increased loss of marginal bone was reported by many authors, with 2–9 mm variations for a period of 3 years after implant surgery [16]. According to Tanaka [17], early failures are more frequent. In the studies, all failures occurred >1 year after implant placement.

In the present series, a case of loss of osseointegration resulted in extensive ORN at a rate of 2.5%. Treatment of ORN required a subsequent free vascularized bone transfer reconstruction. This patient had been treated for a mouth floor lesion in the past and had received a postoperative radiation dose of 64 Gy (See Patient 3, Tab. I). This implant failed 1 year previously, and a reimplantation was proposed because of the impossibility of prosthetic rehabilitation without bone anchorage. Thus, there were two interventions on adjacent parasymphyseal mandibular bone sites. The patient had reverted to smoking regularly despite tobacco counseling. The risk of triggering ORN following implant placement was estimated to be 1.6%–5% [9,16,18,19]. Some authors advocate the use of hyperbaric oxygen therapy before and after implantation to stimulate or optimize healing and decrease ORN risk [20,21]. Others believe that the risk/benefit/cost ratio is not sufficiently favorable. More recently, the use of low-intensity pulsed ultrasound to increase healing capacity has been advocated [22]. Animal studies are currently underway [23].

Conclusion

It is widely accepted that the use of implant techniques in cancer patients is sometimes essential to ensure functional prosthetic rehabilitation. This retrospective study, which was conducted on patients who had specifically received oral radiotherapy, confirmed that it was a reliable therapeutic treatment for radiation doses of 45–50 Gy. However, the small number of patients in this study prevents the extrapolation of results to larger populations, considering the significant morbidity and lower success rate than patients who were not irradiated. Thus, the inherent risk of a past history of radiotherapy must be taken into account. The use of software like Dentalmaps® [24] allows a better evaluation of the doses received at potential implantation sites. This software is based on the automatic segmentation and delineation of the dental zones, making it possible to estimate the dose received at different points of the dental arch to the nearest 2-Gy fraction. However, the software is expensive, the work is laborious, and this device cannot be routinely used. Considering that health organizations are responsible for the cost management of implants in patients with cancer of UADT, there will be a definite increase in the indications for implantation [25]. It is up to the members present at the multidisciplinary consultation meetings to evaluate the benefit/risk ratio on a case-by-case basis.

2018-10-16T13:03:44-07:00October, 2018|Oral Cancer News|

Ask the Dentist: Cancer patients should be aware how radiotherapy can affect saliva

Source: www.irishnews.com
Author: Lucy Stock

SALIVA – we normally give little thought to our spit but we definitely notice when it’s not there. Every day in the UK 31 people are diagnosed with a head and neck cancer. With increasing numbers of people undergoing radiotherapy for head and neck cancers there are more people living with the side-effects of not having enough saliva.

Dry mouth, termed xerostomia, is common after radiotherapy. It’s not only extremely uncomfortable, it makes speaking and swallowing more difficult and alters how things taste. Food can taste saltier, metallic; you can lose your sense of taste totally; and perhaps even worse, foods can taste foul, like sour milk.

Not being able to chew and swallow easily can reduce how much you eat and how well you eat, leading to weight loss and poor nourishment.

Saliva performs numerous jobs. It starts digestion by breaking down food and flushes food particles from between the teeth. Crucially, saliva contains minerals such as calcium and phosphate that keep teeth strong. So no saliva means that teeth decay rapidly and extensively. Even voice quality can change.

Without enough saliva, bacteria and other organisms in the mouth take the opportunity to grow uncontrollably. Nasty sores and mouth infections, including yeast thrush infections, are run-of-the-mill.

Luckily a dry mouth is usually a temporary nuisance that clears up in about two to eight weeks but it can take six months or longer for the salivary glands to start producing saliva again after radiotherapy ends.

In a 2017 study, out of several treatments tested, the drug pilocarpine gave the most significant improvement in dry mouth following radiotherapy. However, you may experience a side effect, albeit short lived, from this medication and it can take a couple of months to work.

Artificial salivas are available as lozenges, sprays and gels, the downside being that their benefits last only a few hours. The Biotene range is specially designed to help relieve dry mouths and includes toothpastes, mouthwashes and gels to give comfort and protect the teeth.

You can buy small atomiser spray bottles from most chemists and fill them with water or fluoride mouthwash. If you cannot swallow, your nurse or doctor can give you a nebuliser to moisten your mouth and throat. Always visit your dentist before cancer treatments to maximise the health of your mouth.

Relieve a dry mouth by:

  • Sipping water often
  • Avoiding drinks with caffeine which dry out the mouth
  • Chewing sugarless gum
  • Avoiding spicy or salty foods, which may cause pain
  • Avoiding tobacco or alcohol
  • Using a humidifier at night.
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