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Identification and characterization of cancer stem cells in human head and neck squamous cell carcinoma

Sun, Mar 16, 2014


Author: staff

Current evidence suggests that initiation, growth, and invasion of cancer are driven by a small population of cancer stem cells (CSC). Previous studies have identified CD44+ cells as cancer stem cells in head and neck squamous cell carcinoma (HNSCC).

However, CD44 is widely expressed in most cells in HNSCC tumor samples and several cell lines tested. We previously identified a small population of CD24+/CD44+ cells in HNSCC.

In this study, we examined whether this population of cells may represent CSC in HNSCC.

CD24+/CD44+ cells from HNSCC cell lines were sorted by flow cytometry, and their phenotype was confirmed by qRT-PCR. Their self-renewal and differentiation properties, clonogenicity in collagen gels, and response to anticancer drugs were tested in vitro.

The tumorigenicity potential of CD24+/CD44+ cells was tested in athymic nude mice in vivo.

Our results show that CD24+/CD44+ cells possessed stemness characteristics of self-renewal and differentiation. CD24+/CD44+ cells showed higher cell invasion in vitro and made higher number of colonies in collagen gels compared to CD24-/CD44+ HNSCC cells.

In addition, the CD24+/CD44+ cells were more chemo-resistant to gemcitabine and cisplatin compared to CD24-/CD44+ cells. In vivo, CD24+/CD44+ cells showed a tendency to generate larger tumors in nude mice compared to CD24-/CD44+ cell population.

Our study clearly demonstrates that a distinct small population of CD24+/CD44+ cells is present in HNSCC that shows stem cell-like properties. This distinct small population of cells should be further characterized and may provide an opportunity to target HNSCC CSC for therapy.

Source: BMC Cancer 2014, 14:173
Author: Jing HanToshio FujisawaSyed R HusainRaj K Puri

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Throat cancer survivor celebrates life after trans-oral robotic surgery

Fri, Mar 7, 2014


Author: staff

When Charlie Guinn sits down to eat with his lovely wife of 39 years, he thoroughly enjoys each bite. It’s not just the food; the entire experience is a celebration. Just over a year ago, Mr. Guinn learned that he had stage IV throat cancer. For him, just surviving would have been an accomplishment — so swallowing again at a meal with a loved one is truly something special.

The American Cancer Society estimates that in 2013 over 41,000 people in the U.S. were diagnosed with cancer of the oral cavity and pharynx and almost 8,000 died from the disease. But Mr. Guinn would be the first to say that he is one of the lucky ones. He is one of the first patients to undergo trans-oral robotic surgery (TORS) at the University of New Mexico Hospital. And the results have been stunning.

Mr. Guinn first discovered the lump in his throat while shaving. When it was still there a week later, he went to an urgent care center where he was immediately referred to an Ear, Nose and Throat physician. The physician ran a number of tests including a biopsy. When the results came back, the physician referred Mr. Guinn to Nathan Boyd, MD, at the University of New Mexico Cancer Center. It had been only a week and a half from that fateful visit to urgent care.

Mr. Guinn recalls, “When I first got there to see Dr. Boyd, one of the nurses told me, ‘You really hit the lottery because you have some of the finest doctors working on you.’ And I agree. Dr. Boyd is one of the most fantastic people I’ve ever met.” Dr. Boyd, an Assistant Professor in the Department of Surgery, Division of Otolaryngology at the UNM School of Medicine, is one of the first two physicians in New Mexico to offer TORS. The other physician, Andrew Cowan, MD, PhD, is also an Assistant Professor in the Department of Surgery, Division of Otolaryngology at the UNM School of Medicine and initiated and launched the surgical program in early 2013.

After his initial consultation with Dr. Boyd, in which he learned about his surgical options, Mr. Guinn consulted with two other physicians at the UNM Cancer Center that same day. He met with his oncologist, Elizabeth McGuire, MD, an Associate Professor in the Department of Internal Medicine, Division of Hematology/Oncology; and with his radiation therapy physician, William Thompson, MD, a Staff Physician in the Department of Internal Medicine, Division of Hematology/Oncology.

The physician team took Mr. Guinn’s preferences into account and agreed to offer him the TORS procedure. Dr. Boyd explained to Mr. Guinn that they would need to complete at least one exploratory surgery first. Mr. Guinn agreed. He recalls that meeting with a laugh and says, “Dr. Boyd told me, ‘My goal for you is, in one year, to have a [Blake’s] Lotaburger with cheese and green chile.’”

Three weeks later, Dr. Boyd completed three TORS procedures on Mr. Guinn and the tumor was out. But because the tumor cells had spread to the lymph nodes, even bursting one of them, Mr. Guinn’s UNM Cancer Center physician team decided to recommend chemotherapy and radiation as a preventive measure to make sure no cancer cells were lurking. Mr. Guinn did not like the additional treatments but knew they were necessary. “The worst experience for me was the radiation,” he says. He experienced some third-degree burning during his course of treatment, but has healed now. He shrugs off the experience saying it’s nothing compared to what burn victims go through.

His chemotherapy experience was a little better. Mr. Guinn didn’t feel like eating very much and he lost weight. “That was the positive of all this,” he laughs. “I do not recommend the diet, but it was the greatest thing.” Another side effect was his hair changing color. “I didn’t lose my hair. I’ve been silver and grey since my late 20s and now my hair is black. At first, I was mad.” But, he’s now accustomed to the darker hair.

Mr. Guinn reflects on what the experience of the past year has brought him. “It’s made me understand what other people go through and what their families go through,” he says. “And I realize that it’s not talking about it but just asking: How are you feeling? What can I do for you?”

Additionally, he and wife have gotten closer. “We’ve been married for 39 years. And we never thought we could get closer.” They are planning a celebratory vacation together.
Finally, Mr. Guinn credits his recovery to his faith, positive attitude, and the people around him who helped him keep that positive attitude. His family was with him at every single appointment. His family and friends sent their prayers and cards, meals, and other helpful items. And his entire treatment team at the UNM Hospital and the UNM Cancer Center gave him the confidence that he would pull through. “Ever since I met Dr. Boyd, not once did I think I was going to die,” he says. “I tell people, you don’t need to go anywhere. These people will take good care of you.”

At his latest visit recently, Mr. Guinn gave Dr. Boyd a gift card to Blake’s Lotaburger. He laughs as he recalls the look on his surgeon’s face. “I told him, ‘Have one on me!’

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Brits call for smoking in films to be stubbed out

Fri, Mar 7, 2014


Author: staff

After a record night of success for British talent at the Oscars, a new poll reveals a majority of us would like to stub out smoking in films watched by children.

In a survey conducted by oral health charity the British Dental Health Foundation, more than two thirds (67 per cent) said they thought films featuring actors smoking should receive the highest classification rating, suitable only for adults. According to the British Board of Film Classification, rated-18 films currently allow scenes of drug-taking, provided ‘the work as a whole must not promote or encourage drug misuse’. The film board makes no reference to smoking or alcohol misuse, two of the leading risk factors for mouth cancer.


Rita Hayworth

One in five people in the UK smoke, and the habit is still considered the leading cause of mouth cancer. But while many of us are aware of the damage that smoking does to our lungs, the danger to our mouths remains relatively unknown. Smoking helps to transforms saliva into a deadly cocktail that damages cells in the mouth and can turn them cancerous. As alcohol aids the absorption of tobacco into the mouth, those who smoke and drink to excess are up to 30 times more likely to develop the disease.

Chief Executive of the British Dental Health Foundation, Dr Nigel Carter OBE, urged the film board to consider its policy on films depicting smoking. Dr Carter said: “The risks of smoking have been well documented for many years, yet for many young people the message still isn’t getting through. Children see movie stars as role models. If they are smoking, children are more likely to take up the habit. The same applies to sports stars, people we see on every day TV and even parents. By re-classifying films containing smoking scenes, it could lead to a drop in the number of young children taking up the habit.

“Tobacco use is still the leading cause of mouth cancer, a disease that claims more lives than cervical and testicular cancer combined. Through campaigns such as Mouth Cancer Action Month in November and No Smoking Day on Wednesday 12 March, it is vital people take the warnings about smoking on board. Mouth cancer is the most severe outcome, but it can lead to many oral health problems such as tooth staining, gum disease and tooth loss.

“It is really important that everyone knows the warning signs for mouth cancer. They include mouth ulcers which do not heal within three weeks, red and white patches in the mouth and unusual lumps or swellings in the mouth. Our message to everyone is ‘If in doubt, get checked out’.”

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Protein Deters Head, Neck Cancer Growth, Study Shows

Mon, Mar 3, 2014


Source: JADA (Journal of the American Dental Association)

Scientists at the National Institute of Dental and Craniofacial Research found that blocking a certain protein inhibited the proliferation of head and neck squamous cell carcinoma, according to a study published in the February issue of Molecular Oncology.

In an experiment involving tissue samples of hundreds of head and neck cancer patients, an NIDCR team led by Silvio Gutkind, PhD, chief of NIDCR’s Oral and Pharyngeal Cancer Branch, found that p38 kinase was active in most samples. They reported that the most malignant tissue samples had the highest activity of p38, and the least malignant samples had the lowest p38 activity. The normal oral tissue used as a control had no p38 activity.

When researchers turned off p38 activity in human oral cancer cells and transplanted these cells into laboratory mice, they found that the oral cancer cells without p38 activity were smaller than those with p38 activity. In addition, turning off p38 activity lessened the growth of new blood vessels, which cancers rely on for growth and the ability to spread to other parts of the body.

In the next phase of the study, they tested SB203580—a drug that is known to block p38 activity. SB203580 reduced the growth of head and neck cancer cells in the laboratory. When the NIDCR team then used SB203580 to treat human head and neck cancers that had been transplanted into lab mice, they found that SB203580 made the cancers smaller.

The next step, Dr. Gutkind says, is to test a new generation of drugs that inhibit p38.

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

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Improving QOL in head and neck cancer as survival improves

Fri, Feb 28, 2014


Author: Zosia Chustecka

In patients undergoing radiation treatment for head and neck cancer, reducing the radiation to organs not affected by cancer is key to improving quality of life post-treatment.

Several studies presented here at the 2014 Multidisciplinary Head and Neck Cancer Symposium described new approaches to sparing radiation delivered to the salivary glands and to the voice box, without any loss of cancer control, but with a reported reduction in adverse effects, such as xerostomia (dry mouth), and an anticipated reduction in loss of voice and speech quality.

Improvements in such outcomes are becoming increasingly important as the epidemiology of head and neck cancer is changing, and the increase in human papillomavirus-positive disease means that patients are being diagnosed their 50s and will, in many cases, go on to live for decades after their definitive cancer treatment, researchers commented at a press briefing.

Xerostomia can make it difficult to speak, as well as chew and swallow, and can lead to dental problems. “Dry mouth might seem trivial, but it actually has a significant effect on quality of life,” commented Tyler Robin, PhD, an MD candidate in his final year at the University of Colorado Medical School in Denver.

To reduce this adverse effect, intensity-modulated radiation techniques are already directing the beam away from the parotid gland, which is responsible for stimulated saliva production, for example during eating. But for the rest of the time, saliva is produced unstimulated from the submandibular gland. “This gland actually produces the majority of saliva for the majority of the day,” he said.

“Historically, however, there had been hesitation to spare the submandibular gland from radiation because there are lymph nodes near the gland that also end up not getting treated,” he said. “While this seems worrisome because head and neck cancer spreads through the lymph nodes, it is well established that the risk of cancer involvement in the lymph nodes near the submandibular gland is exceedingly low, yet the benefit of sparing the gland for a patient’s quality of life is high.”

Dr. Robin presented data from 71 patients with advanced head and neck cancer who were treated with radiation that spared the contralateral submandibular gland in a collaborative study conducted at the University of Colorado and the Memorial Sloan-Kettering Cancer Center in New York City. The mean radiation dose delivered to the contralateral gland was 33.04 Gy./p>

At a median follow-up of 27.3 months, none had had cancer recurrences in the spared area.

This is preliminary evidence that submandibular gland-sparing radiotherapy is feasible technically, and that it is safe even in advanced-stage node-positive cancers, the researchers conclude. They suggest that these outcomes data “offer significant promise for decreasing morbidity.”

More data on this submandibular gland-sparing approach were presented at the meeting by Moses Tam, BS, an MB candidate in his final year at New York University School of Medicine in New York City, who was also an author on the previous presentation.

He reported data from 125 patients (median age, 57 years) with oropharyngeal cancer (53% base of tongue, 41% tonsil, 6% other), all of whom had node involvement (16% N1, 8% N2A, 48% N2B, and 28% N2C).

All patients underwent chemoradiation, but some patients had sparing radiation, with a reduction of radiation treatment volume to the submandibular (level 1B) lymph nodes, while the remainder had radiation without sparing.

The sparing approach significantly reduced the dose of radiation to the submandibular salivary glands (from 70.5 Gy to 63.9 Gy in the ipsilateral gland, and from 56.2 Gy to 43.0 Gy in the contralateral gland), and also to the oral cavity (from 45.2 Gy to 36.1 Gy; all P < .001).

Both groups of patients had a similar 2-year local regional control rate — 97.5% with sparing radiation and 93.8% with nonsparing radiation — indicating a low rate of tumor recurrence at the original tumor site.

However, those who received the sparing radiation had significant improvement in both patient-reported xerostomia summary scores ( P = .021) and observer-rated xerostomia scores ( P = .006), compared with the other group.

“Our data show that it is safe to spare the lymph nodes in oropharyngeal cancer from radiation,” Tam commented. This approach reduces the radiation dose to several nearby salivary organs, and therefore causes less damage to a patient’s post-treatment salivary function.

Effects on Voice and Speech Under-recognized

In contrast to the attention that has been focused on chronic mouth dryness and swallowing difficulties as complications of radiotherapy, relatively little attention has been paid to treatment-related changes in voice and speech quality, commented Jeffrey Vainshtein, MD, chief resident in the Department of Radiation Oncology at the University of Michigan in Ann Arbor.

In fact, physicians tend to underestimate the detrimental effects of head and neck radiation on this aspect of patients’ quality of life, he commented, and presented data showing a wide discrepancy between the reports from patients as compared to physicians on a voice and speech quality assessment tool.

The finding comes from a study conducted in 91 patients with stage III or IV oropharyngeal cancer who had participated in trials at the University of Michigan and been treated with definitive concurrent chemotherapy (weekly carboplatin and paclitaxel) and organ-sparing intensity-modulated radiation therapy (IMRT).

Patient-reported results show a maximal decrease in voice and speech quality at 1 month, with 41% to 68% of patients (using 2 different questionnaires) reporting worse quality than pretreatment baseline levels. Voice and speech quality returned to baseline levels by 12 to 18 months, but not in all patients. At 12 months, 28% to 33% of patients continued to report lower voice and speech quality.

In contrast, physicians reported that larynx toxicity was rare, and reported grade 1 toxicity in 5% of patients at 6 months, and in none at 1 and 2 years.

“It’s interesting to see this physician and patient disconnect,” commented Mitchell Machtay, MD, chair of radiation oncology at Case Western Reserve University in Cleveland, who moderated the press conference.

Dr. Vainshtein said that the degree of disconnect was “quite surprising,” but added that this is not unique to this study or to oncology, and indeed is seen throughout medicine. He suggested that physicians may miss the subtleties of changes in quality of life, and also some patients may not mention symptoms when talking with their doctor, but once they are asked in detail in a structured questionnaire, the results can be quite informative. He also said that more emphasis should be, and in fact is already being, placed on patient-reported outcomes in clinical trials.

Further analysis showed that the mean radiation dose to the voice box (glottic larynx) was independently associated with poor voice quality, while patient-perceived speech difficulties were related to the radiation dose received by both the voice box and the oral cavity.

These findings, from the largest prospective study of this issue to date, support limiting the mean radiation dose to the glottic larynx to less than 20 Gy during whole-neck IMRT for head and neck cancer when the larynx is not a target, the researchers conclude.

Minimizing the radiation dose is likely to reduce voice and speech problems, and thus improve post-treatment quality of life, Dr. Vainshtein commented.

Notes: The authors have disclosed no relevant financial relationships.
Source: 2 2014 Multidisciplinary Head and Neck Cancer Symposium (MHNCS): Abstracts 12 (Robin), 121 (Vainshtein), 139 (Tam). Presented February 21, 2014.

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Mouth bacteria trigger oral cancer

Fri, Feb 28, 2014


Author: Tim Sandle

Chemicals released from two bacteria that cause gum disease can incite the growth of deadly lesions and tumors in the mouth, trigger oral cancer. This is according to a new study carried out by Case Western Reserve University.

High levels of certain bacteria found in the saliva of people are associated with the risk of oral cancer. The researchers were keen to understand why most people never develop oral cancer and what it is that protects them. Their answer related to most people not carrying a certain type of bacteria in their mouths.

The cancer of concern is Kaposi’s sarcoma-related (KS) lesions and tumors in the mouth. The bacteria associated with this are the species Porphyromonas gingivalis and Fusobacterium nucleatum. These species are associated with gum disease.

For the research, scientists recruited 21 patients, dividing them into two groups. All participants were given standard gum-disease tests. The first group of 11 participants had an average age of 50 and had severe chronic gum disease. The second group of 10 participants, whose average age was about 26, had healthy gums. The bacteria were common to those with gum disease.

By carrying out further tests, the researchers found that the bacteria produce fatty acids and these fatty acids then allowed oral cancer causing viruses to grow. The discovery could lead to early saliva testing for the bacteria. When such bacteria are found the mouth of a patient could be treated and monitored for signs of cancer and before it develops into a malignancy.

The findings have been reported in The Journal of Virology, in a paper titled “Short Chain Fatty Acids from Periodontal Pathogens Suppress HDACs, EZH2, and SUV39H1 to Promote Kaposi’s Sarcoma-Associated Herpesvirus Replication.”

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Contralateral submandibular gland-sparing radiation safe, effective in head, neck cancers

Wed, Feb 26, 2014


Published: February 24, 2014


Sparing the contralateral submandibular gland with low doses of radiation therapy appeared safe and effective among patients with locally advanced head and neck cancers, according to study results presented at the Multidisciplinary Head and Neck Cancer Symposium.

“Historically … there has been hesitation to spare the submandibular gland from radiation because there are lymph nodes near the gland that also end up not getting treated,” researcher Tyler Robin, PhD, an MD candidate at the University of Colorado School of Medicine, said in a press release. “While this seems worrisome because head and neck cancer spreads through the lymph nodes, it is well established that the risk of cancer involvement in the lymph nodes near the submandibular gland is exceedingly low, yet the benefit of sparing the gland for a patient’s quality of life is high.”

Robin and colleagues evaluated data from 71 patients who underwent contralateral submandibular gland-sparing radiation therapy at the University of Colorado Cancer Center or Memorial Sloan-Kettering Cancer Center. The median age of patients was 55 years. About half of patients were current or former smokers, and half were never smokers.

Nearly 50% of patients had lesions involving the base of the tongue. About 80% of patients had N2b or greater disease, and 90% of patients had overall stage IV disease.

Researchers classified contralateral submandibular gland sparing as mean radiation doses to the contralateral submandibular gland of ≤39 Gy. The mean radiation dose to the contralateral submandibular gland of all patients in the study was 33.04 Gy.

Median follow-up was 27.3 months. At this time, no patients experienced disease recurrences in the contralateral level Ib lymph nodes.

“It is important to consider treatment side effects alongside treatment benefit, and overall, our goal is to decrease side effects associated with radiation treatment without undertreating a patient’s cancer,” Robin said. “With modern advances in radiation therapy, it is possible to eloquently treat cancers while avoiding surrounding normal tissues. Our study is a prime example of how we can safely spare normal tissues in appropriate patients in order to decrease treatment side effects.”



* This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
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HPV-Positive Oropharyngeal Patients Show Overall Higher Survival Rate Compared to HPV-Negative Patients

Tue, Feb 25, 2014


Published: February 20, 2014
By: Michelle Kirkwood

Scottsdale, Ariz., February 20, 2014—A retrospective analysis of oropharyngeal patients with recurrence of disease after primary therapy in the Radiation Therapy Oncology Group (RTOG) studies 0129 or 0522 found that HPV-positive patients had a higher overall survival (OS) rate than HPV-negative patients (at two years post-treatment, 54.6 percent vs. 27.6 percent, respectively), according to research presented today at the 2014 Multidisciplinary Head and Neck Cancer Symposium.

The analysis included 181 patients with stage III-IV oropharyngeal squamous cell carcinoma (OPSCC) with known HPV status (HPV-positive = 105; HPV-negative = 76), and cancer progression that was local, regional and/or distant after completion of primary cisplatin-based chemotherapy and radiation therapy (standard vs. accelerated fractionation (AFX)) in RTOG 0129 or cisplatin-AFX with or without cetuximab in RTOG 0522. Tumor status was determined by a surrogate, p16 immunohistochemistry.

Median time to progression was virtually the same for HPV-positive and HPV-negative patients (8.2 months vs. 7.3 months, respectively). Increased risk of death in univariate analysis was associated with high tumor stage at diagnosis (T4 vs. T2-T3), fewer on-protocol cisplatin cycles (≤1 vs. 2-3) and distant vs. local/regional recurrent (for all, hazard ratios (HRs) >2.0 and p<0.05). Risk of death after disease progression increased by 1 percent per cigarette pack-year at diagnosis. Rates were estimated by Kaplan-Meier method and compared by log-rank. HRs were estimated by Cox proportional hazards models and stratified by treatment protocol.

In addition, HPV-positive and HPV-negative patients who underwent surgery after cancer recurrence also experienced improved OS compared to those who did not undergo surgery. (The effect may have been more pronounced among HPV-positive than HPV-negative patients.) Recurrence is most commonly in the lungs for both groups of patients.

“Our findings demonstrate that HPV-positive OPSCC patients have significantly improved survival after progression of disease when compared with HPV-negative patients. Median survival after disease progression was strikingly longer for HPV-positive than HPV-negative patients,” said lead author Carole Fakhry, MD, MPH, assistant professor in the Department of Otolaryngology Head and Neck Surgery at Johns Hopkins Medicine in Baltimore. “These findings provide us with valuable knowledge to better counsel and treat patients.”


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


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Gland-sparing technique safe in tonsillar, tongue cancers

Tue, Feb 25, 2014


Source: Oncology Report
Published: February 24, 2014
By: Neil Osterweil


SCOTTSDALE, ARIZ. – Although radiation oncologists have typically worried that, in patients with oral cancers, leaving contralateral submandibular glands untreated could lead to tumor involvement of nearby lymph nodes, those worries may soon be put to rest, suggest results of a small retrospective study.

Among 71 patients with locally advanced cancers of the tongue base or tonsils who underwent radiation therapy that avoided targeting the contralateral submandibular glands, there were no cancer recurrences in contralateral level 1B nodes after a median 27.3 months of follow-up, reported Dr. Tyler Robin of the University of Colorado at Denver, Aurora.

“We’re interested in sparing the contralateral submandibular gland because we’re interested in minimizing xerostomia. Xerostomia is a significant morbidity of head and neck cancer radiotherapy, and it has substantial impact on patient quality of life,” Dr. Robin said at the Multidisciplinary Head and Neck Cancer Symposium.

Intensity-modulated radiation therapy (IMRT) allows treatment beams to be shaped to avoid the parotid glands with no subsequent increase in regional lymph node failures and preservation of parotid salivary flow. But patient-reported xerostomia and quality-of-life outcomes with parotid-sparing techniques have been mixed, Dr. Robin said.

“Interestingly, an earlier study looking at predictors of xerostomia found that dose to the submandibular gland was a stronger predictor of xerostomia than dose to the parotids, and this may be because of the role of the submandibular gland in unstimulated salivary flow,” he said.

The submandibular gland is located near level IB lymph nodes, but the risk of contralateral level IB involvement in oropharyngeal (OP) cancers is low, on the order of 0%-2%. Gland-sparing therapy with IMRT has previously been shown to mitigate xerostomia and to be safe, but primarily in patients with early-stage disease, prompting the investigators to examine whether it would also be safe and effective in patients with locally advanced tumors.

The question is particularly relevant at a time when the epidemiology of OP cancers is shifting toward patients who are positive for the human papillomavirus, who are more likely to have good therapeutic outcomes and who may live for many decades beyond an initial diagnosis, Dr. Robin said at the symposium cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology.

His team reviewed records of 71 patients treated for primary OP cancers at the University of Colorado and at Memorial Sloan-Kettering Cancer Center in New York.

In all, 40 patients had tonsillar cancers, 28 had base-of-tongue lesions, and 3 had cancers involving both sites.

They considered gland-sparing procedures as those in which total doses delivered to the contralateral submandibular gland during bilateral neck radiotherapy were not more than 39 Gy.

Of the 71 patients, 61 (85.9%) had stage IVA disease, 6 (8.5%) had stage III cancers, and 3 (4.2%) had stage IVB disease. The majority of patients had significant nodal involvement, with 46 (64.8%) having stage N2b; 7 (9.9%) N2c; and 3 (4.2%) having staging N3 disease.

The respective mean and median doses to the contralateral glands were 33.04 and 34.21 Gy.

At median follow-up of 27.3 months, there were 12 treatment failures: 1 local, 6 regional, and 5 distant failures. However, there were no cases of disease recurrence in contralateral level IB nodes, the investigators found. There was, however, one documented case of recurrence in contralateral level IIa lymph nodes.

“We believe this is evidence that contralateral submandibular gland sparing can be feasible and safe even in advanced node-positive head and neck cancers, including base- of-tongue lesions,” Dr. Robin said,

The data suggest the need for a large prospective trial specifically addressing the safety and efficacy of contralateral submandibular gland-sparing therapy in patients with locally advanced head and neck cancers. Such studies should incorporate existing xerostomia-based quality-of-life assessments and formal sialometry studies, he added.

While the study shows that contralateral submandibular gland sparing is feasible, it raises the question of whether the technique might increase the dose to the muscles of the floor of the mouth, said Dr. Harry Quon of Johns Hopkins University in Baltimore, the invited discussant.

“There is emerging data that our chemoradiation approaches, with long-term follow-up maybe increases [patients’] risk of death, and one hypothesis that has been put forward is chronic aspiration with secondary injury to the lungs,” he said.

Radiation injury to the floor-of-mouth muscles appears to be a significant risk factor for aspiration, indicating that future conformal approaches to treating cancers of the tonsils and tongue base should attempt to avoid delivering excessive doses to the midline mucosa, Dr. Quon said.

The study was internally funded. Dr. Robin and Dr. Quon reported having no financial disclosures.


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


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Effects of Chemoradiation on Voice and Speech Quality of H&N Cancer Patients

Mon, Feb 24, 2014


Source: Med Page Today
Published: February 23, 2014
By: Charles Bankhead


SCOTTSDALE, Ariz. — Patients with oropharyngeal cancer reported significant voice and speech impairment for up to 2 years after chemoradiation therapy, but most of their doctors saw no evidence of it, data from a prospective study showed.

Two years after treatment, a fourth of patients said their voice and speech remained below baseline levels, whereas none of their clinicians noted any impairment. At no time did as many as 10% of clinicians report patients with speech and voice issues, whereas the proportion of patients reporting problems ranged as high as 56%.

The likelihood of patient-reported difficulties with oral communication increased with the radiation dose to the glottic larynx, reported Jeffrey M. Vainshtein, MD, and colleagues at the Multidisciplinary Head and Neck Cancer Symposium.

“Our findings highlight the critical role of patient-reported outcomes in identifying areas of improvement of our current therapies, which may ultimately translate into improvements in quality of life for our patients,” Vainshtein, of the University of Michigan in Ann Arbor, said during a press briefing.

Dysphagia and xerostomia are recognized adverse effects of chemoradiation for head and neck cancer and have been studied extensively in recent years. In contrast, a paucity of information exists relative to the effects of chemoradiation on voice and speech quality, Vainshtein said.

To examine the issue, investigators assessed voice and speech outcomes in 93 patients who underwent chemoradiation for oropharyngeal cancer, using intensity-modulated radiation therapy (IMRT). At baseline, and then every 3 to 6 months after finishing treatment, patients completed two validated questionnaires: Head and Neck Quality of Life (HNQOL) and University of Washington Quality of Life (UWQOL).

At the same intervals, the patients’ physicians reported their assessments in accordance with the Common Terminology Criteria for Adverse Events.

All of the patients had locally advanced stage III/IV oropharyngeal cancer and received treatment in two clinical trials of organ-sparing IMRT. Radiation therapy protocols were designed to minimize the radiation dose to the pharyngeal constrictors, salivary glands, oral cavity, glottic larynx, supraglottic larynx, and esophagus.

Vainshtein and colleagues analyzed patient questionnaires to identify factors associated with voice and speech impairment, in addition to the frequency of impairment.

By the HNQOL communication domain and speech impairment domain of the UWQOL, radiotherapy-induced speech impairment reached a maximum in the first month after treatment. Impairment then decreased in subsequent assessments, stabilizing at 12 to 18 months.

The proportion of patients reporting post-treatment speech and voice impairment followed a time pattern consistent with speech impairment reflected in answers to the questionnaires. By the HNQOL, 68% of patients said their voice and speech quality were impaired versus baseline, decreasing to 56% at 3 months, 46% at 6 months, 33% at 12 months, 31% at 18 months, and 24% at 24 months.

By the UWQOL, the proportion of patients reporting worsening of voice and speech quality after treatment was 41%, 26%, 29%, 28%, 15%, and 22% at the assessments from 1 to 24 months after finishing therapy.

In contrast, few physicians included voice and speech impairment in their adverse event reports. Vainshtein said 7% of physicians reported grade 1 toxicity with respect to worsening of voice and speech at 3 months, 5% at 6 months, and 0% thereafter.

Comparing treatment characteristics and patient-reported voice quality worsening, investigators found an association between radiation dose to the larynx and patient-reported impairment at 6 and 12 months. Reported impairment at 6 months increased from 25% with a cumulative radiation dose of <20 Gy to 59% at >30-40 Gy, 50% at 40-50 Gy, and 64% with laryngeal doses >50 Gy (P=0.02).

A similar pattern emerged from the analysis of 12-month outcomes, as the proportion of patients reporting worsening of voice quality from baseline increased from 10% for laryngeal radiation doses <20 Gy to 63% of patients for cumulative doses >50 Gy (P=0.011).

“We observed similar findings for patient-reported voice quality worsening and speech impairment,” Vainshtein said. “The results were independent of other patient and treatment factors.”

Press briefing moderator Mitchell Machtay, MD, said he found the study eye opening.

“If you looked at radiation dose to larynx, not the area where the tumor was, I was struck by how doses of 20 to 30 Gy, which we don’t normally consider as very toxic high doses that can damage the voicebox, still caused a fair amount of damage,” said Machtay, of University Hospitals Case Medical Center in Cleveland.

The magnitude of disconnect between patient and physician assessments was one of the more surprising findings in the study.

“I don’t think it’s unique to head and neck cancer. I don’t think it’s unique to our study. I don’t think it’s unique to medicine,” Vainshtein said. “I think physicians tend to underestimate the effect of their treatment — whatever it is — on our patients.”

Some adverse effects can be subtle and do not become apparent during conversations with physicians, he continued. When the patients express their sentiments in a more formal manner, such as a questionnaire, the effects do emerge.

Some of the disconnect reflects differences in patients’ approaches to their illness and adverse effects of treatment, said Wade Thorstad, MD, of Washington University in St. Louis.

“There’s a group of patients, when you’re interviewing them about their symptoms, will tell it like it is and really explain things well,” said Thorstad, another participant in the press briefing. “There’s another group that is stoic, and they really underplay their issues before [their physician]. However, when they are filling out a questionnaire about their feelings about quality of life, I think you get a more honest assessment.”


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


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