IMRT provides better QOL in head and neck cancers

AUthor: Miriam E. Tucker

Intensity-modulated radiotherapy is more expensive than 3-D–conformal radiotherapy is and has not been shown to improve standard outcomes in patients with head and neck cancer. But it results in better quality of life. These findings from two studies presented at the Multidisciplinary Head and Neck Cancer Symposium raise the question: Does improved quality of life justify the greater expense of intensity modulated radiotherapy (IMRT), which has been rapidly adopted for the treatment of head and neck cancer?

Because IMRT spares surrounding tissues, it reduces the likelihood of developing xerostomia, noted Dr. Nathan C. Sheets, who presented data on billing charges associated with IMRT, compared with 3-D–conformal radiotherapy (CRT). IMRT is reimbursed at a substantially higher level than CRT, however, and it is unclear how to assess this cost relative to other aspects of care in this population, said Dr. Sheets, a radiation oncology resident at the University of North Carolina, Chapel Hill.

A separate study presented by Dr. Allen M. Chen compared quality of life in patients who received IMRT vs. CRT. “There’s very little data to suggest IMRT is better than non-IMRT using traditional end points. But the question is: How do you define ‘better’?” said Dr. Chen, director of the radiation oncology residency training program at the University of California, Davis in Sacramento.

“IMRT might not particularly involve better cure rates, but it could make a difference in terms of other end points, such as quality of life, which we all know is very important to patients,” he said.

Gap Ranges from $5,000 to $6,000
The cost study analyzed data for 184 patients who had received definitive radiation therapy for head and neck squamous cell cancer at the University of North Carolina at Chapel Hill during 2000-2009 and for whom billing records were available.

The median year of treatment was 2004 for 89 patients treated with CRT, and 2007 for 95 IMRT patients, reflecting the shift to use of IMRT over time. The majority of patients – 87% of CRT and 94% of IMRT – received concurrent chemotherapy. More IMRT patients received positron emission tomography (PET) scans at any point (69% vs. 37%).

Over 36 months’ follow-up, locoregional control was nearly identical for the two patient groups (P = .73). Mean total costs, from the time of diagnosis through the first year of follow-up, were considerably higher for IMRT, at $50,502 vs. $38,977 for CRT. Outpatient costs accounted for the bulk of the difference ($35,418 IMRT vs. $22,696 CRT), whereas inpatient costs were similar, Dr. Sheets reported.

Multivariate analysis showed that factors associated with increased cost of radiotherapy included IMRT, recurrent disease, comorbidities, non-white race, and use of positron-emission scanning. After adjustment for inflation, each of these factors, including IMRT, independently increased the total cost by approximately $5,000-$6000. (Treatment failure was much more expensive, contributing about $14,274 to the total cost.)

Dr. Sheets ended his presentation with the question, “Do the benefits of IMRT outweigh the costs?”

QOL Improves Over 2 Years’ Follow-up
Dr. Chen’s quality of life study addressed that question. The study used the University of Washington Quality of Life instrument (UW-QOL), a previously validated, self-administered questionnaire given to patients returning for follow-up after completion of radiation therapy for head and neck cancer. The University of California, Davis, routinely uses the measure in clinical practice.

Scores on the UW-QOL were retrospectively reviewed for 155 patients with squamous cell carcinomas of the head and neck requiring bilateral neck irradiation for locally advanced disease. Only patients who were clinically without evidence of recurrent disease and with at least 2 years of follow-up were included in the analysis. Definitive radiation therapy was given to 82 patients (53%), while 73 (47%) underwent postoperative treatment.

IMRT was used in 84 patients (54%), with inclusion of the low neck in an extended field. The remaining 71 patients (46%) were treated with 3-D–CRT using opposed lateral fields matched to a low anterior neck field. Concurrent chemotherapy was administered with radiation therapy for 73 patients (47%).

The mean global quality of life scores for the IMRT patients were 67.5 at 1 year and 80.1 at 2 years, compared with 55.4 and 57.0, respectively, for the CRT patients (P less than .001). At 1 year after completion of radiation therapy, the proportion of patients who rated their global quality of life as “very good” or “outstanding” 51% of the IMRT patients, compared with 41% of those treated with CRT (P = .11).

Those numbers became statistically significant at 2 years, with “very good” or “outstanding” quality of life reported by 73% of the IMRT patients and 49% of the CRT group (P less than .001). At last follow-up, 80% of patients treated by IMRT reported that their health-related quality of life was “much better” or “somewhat better,” compared with the month before developing cancer, compared with 61% among patients treated by 3-D–CRT (P less than .001).

On multivariate analysis accounting for gender, age, radiation intent (definitive vs. postoperative), radiation dose, T stage, primary site, use of concurrent chemotherapy, and neck dissection, the use of IMRT was the only variable independently associated with improved quality of life (P = .01).

In 1- and 2-year analyses of factors contributing to the difference in UW-QOL score, only “saliva” was found to be significantly different between IMRT and CRT (P less than .001) for both time points. Other examined factors that did not affect the score included pain, appearance, activity, recreation, chewing, swallowing, speech, mood, and anxiety.

“Treatments for dry mouth are fairly primitive and ineffective at present, so preventing dry mouth is so critical. It’s a huge problem. Imagine not being able to make any saliva. And, there are health consequences with respect to things like oral hygiene and dental caries. There’s a cost associated with chronic dry mouth,” Dr. Chen said in the interview.

Increased Cost Not That Big
The increase in cost with IMRT isn’t that big, Dr. Bhisham Chera, the principal investigator for the cost study and a radiation oncologist at the University of North Carolina said in an interview.

“On average, it was about $5,000-$6,000 more total,” he said. “It is more expensive, but what was shocking to me is that it wasn’t much more expensive as some therapies – like newer chemotherapy drugs, compared to older ones, where there’s a hundred thousand dollar difference in cost and the survival improvement is only a few months.”

“We think the incremental increase in cost is justified because of the improvement in dry mouth. If you really compare it to other therapies such as using transperineal prostatectomy vs. robotic prostatectomy or cisplatin vs. cetuximab chemotherapy, the cost difference is vastly greater,” he added. “Here, the incremental difference is not that much. It is more expensive, but it’s not astronomically more expensive.”

Note: Dr. Sheets, Dr. Chen, and Dr. Chera all stated that they had no disclosures.

2012-02-12T09:20:40-07:00February, 2012|Oral Cancer News|

Review Finds Evidence Lacking for Dry Mouth Remedies

Source: Medscape Today

December 28, 2011 — There is not enough evidence to recommend any topical therapies for dry mouth, but that does not mean that they do not work, according to investigators who published a review of research on the therapies online December 4 in the Cochrane Library.

“There was very little evidence,” said Helen Worthington, PhD, a professor of evidence-based care at the University of Manchester, United Kingdom.

Dr. Worthington and colleagues scoured the literature for randomized controlled trials of topical therapies for dry mouth, or xerostomia. They found 36 studies of treatments such as lozenges, sprays, mouth rinses, gels, oils, chewing gum, and toothpaste.

Xerostomia often results from treatments for head and neck cancer that damage the salivary glands, as well as from Sjögren’s syndrome, an autoimmune disorder that also damages these glands. It is also a common adverse effect of many medications.

The authors cite an estimated prevalence of dry mouth of about 20% in the general population. This percentage may be increasing because people are living longer and suffering from more chronic illnesses for which the treatments can have xerostomia as an adverse effect.

It is possible to feel the sensation of dry mouth without having a clinically reduced saliva flow, the researchers point out.

The treatments in the review broke down into 2 broad categories: saliva substitutes, in which some other substance is intended to perform the role of the patient’s own saliva, and saliva stimulants, which are intended to activate the patient’s own mechanism for producing saliva.

Two of the trials compared saliva stimulants with placebos, 9 compared saliva substitutes with placebos, 5 compared saliva stimulants with saliva substitutes, 18 compared 2 or more saliva substitutes with each other, and 2 compared 2 or more saliva stimulants with each other.

The researchers found convincing evidence that 1 saliva substitute, oxygenated glycerol triester saliva spray, was more effective than another, an electrolyte spray (standardized mean difference, 0.77; 95% confidence interval, 0.38 – 1.15). This corresponded to an approximate mean difference of 2 points on a 10-point visual analog scale in which patients rate their mouth dryness.

However, this evidence did not actually prove that either substitute was useful for treating dry mouth, Dr. Worthington said.

The researchers concluded that an integrated mouth care system (toothpaste, gel, and mouthwash) looked promising, as did oral reservoir devices. Here again, however, the evidence was not quite strong enough to recommend either one.

Asked to comment on the review, Joel Napeñas, DDS, a specialist in saliva disorders at Carolinas Medical Center in Charlotte, North Carolina, told Medscape Medical News that it is still possible to treat dry mouth despite the lack of evidence for a particular therapy.

“There are a lot of nonrandomized controlled trials that do show variable results,” said Dr. Napeñas, who was not involved in the Cochrane review. “Since there is no strong evidence for any individual agent, we are left with trial and error on an individualized basis.”

Dr. Napeñas begins by measuring saliva flow: He has the patient spit into a cup and then asks the patient to suck on something like a piece of wax and spit again to see whether the sucking action increases the patient’s saliva flow.

If the saliva flow increases, this suggests that saliva stimulants may work. Barring contraindications, therefore, Dr. Napeñas prescribes systemic saliva stimulants, usually pilocarpine or cevimeline, often in combination with topical stimulants.

If the experiment does not increase saliva flow, Dr. Napeñas instead recommends various saliva substitutes. He also typically recommends that patients try a variety of topical therapies to see what works best. “Biotene-type products are some of the first we would go to,” he said.

Frequently sipping water and sucking on ice can help many patients, he said. He advises patients to avoid caffeine and alcohol, which can worsen symptoms, and he pointed out that patients with xerostomia should avoid many commercial mouth rinses because they contain alcohol.

Dr. Napeñas also initiates preventive measures to prevent caries, including topical fluoride, prescription fluoride products, and frequent recalls, because patients with low saliva flow are at high risk for caries.

“It’s a very difficult condition to treat,” he said. “The way I approach it is to throw everything I can at it.”

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

2011-12-28T15:56:36-07:00December, 2011|Oral Cancer News|

Consider dental issues before beginning cancer treatment

Author: Lacey Meyer

Dentists advise resolving tooth and gum issues before starting cancer treatment.

Bettye Davis admits she has never had very good teeth. But when she received a diagnosis of salivary gland cancer, she was surprised that her oncologist recommended she visit a dentist before beginning radiation treatments to her jaw.

“When we first saw her, she still had quite a few teeth, but she had severe periodontal disease and severe bone loss,” says Dennis Abbott, DDS, Davis’ dentist. Knowing radiation would do more damage, he recommended removing the remainder of her teeth and allowing time to heal before she began 33 radiation treatments.

“We knew that if we took the teeth out after radiation, we risked the bone not healing well, which would have meant osteonecrosis, dead bone in her mouth, and lots of systemic problems.”

According to the National Cancer Institute, eliminating pre-existing dental and mucosal infections and instituting a comprehensive oral hygiene protocol before and throughout therapy can reduce the severity and frequency of oral complications from cancer therapy. Abbott says the NCI recommendations, as well as an increasing number of studies, are bringing more recognition to the importance of dental issues before, during and after cancer treatment.

A Proactive Approach
Abbott’s goal is to help patients maintain healthy teeth and reduce the risk of future infection with an oral care plan that eliminates or stabilizes disease that could produce complications during or following therapy. These complications can range from irradiated bone and gums not healing properly to an oral bacterial infection spreading throughout the body due to chemotherapy-induced immunosuppression.

Radiation to the head and neck area can also cause severe dry mouth (xerostomia) and loss of the protective effects of saliva, which accelerates existing tooth decay and can damage tiny blood vessels in the bone that deliver nutrients and oxygen that allow the bone to grow. So any tooth extractions or invasive dental procedures in irradiated bone are likely to result in slow healing, leading to pain and infection.

Oral complications may be acute (developing during therapy) or chronic (developing or continuing long after therapy), with the most common and significant being oral mucositis (inflammation and ulcers in the lining of the mouth), salivary gland dysfunction, taste dysfunction, pain and dry mouth. Limited or no saliva can lead to increased risk of infections in the mouth, gum disease and dental disease, which can progress rapidly and be difficult to control.

Available medications to stimulate saliva production rely on residual salivary gland function, if enough function remains. Mouth gels, rinses and sprays can moisturize the mouth, but unlike natural saliva, they don’t contain antibodies; growth and repair factors; fluoride; and calcium phosphates that help keep teeth healthy and strong.

Abbott says this means patients must be proactive in caring for their teeth to prevent cavities. Topical antimicrobials or antiseptics can also help control infections, including dental decay related to acid-producing bacteria.

Oral Health and Overall Health
With radiation therapy directed at her salivary glands, Davis, 73, experienced extreme dry mouth, especially at night. But, she says, a mint-flavored antioxidant topical gel Abbott prescribed, AO ProVantage, effectively relieved this symptom. “It has really helped because it keeps your mouth refreshed, plus it helps you have more moisture in your mouth,” Davis says.

The decision to extract teeth prior to radiation, Abbott says, is based on the health of the tooth, the condition of the gums and bone around the tooth, the amount of radiation the bone around the tooth is scheduled to receive and the area that will be radiated. Gum disease is a cause for tooth extraction prior to therapy. Other causes include problems with previous root canals, tooth fractures and broken fillings that can’t be adequately restored.

“You can’t dismiss oral health because it affects systemic health,” Abbott says. “The mouth has a huge amount of bacteria, and if it’s not taken care of, there is the risk of that bacteria getting into the bloodstream.”

Catching Up to Get Ahead
The American Dental Association recommends all cancer patients schedule a dental exam at least two weeks before beginning treatment. This should involve a full comprehensive exam, gum probing around every tooth and X-rays. It may also include removal of local sites of irritation, such as broken teeth, or identifying chronic infections, such as gum disease.

“Those conditions need to be managed up front because we are very limited after treatment and the complication risk is so significant that not doing it before can lead to significant difficulties after,” says Joel Epstein, DMD, MSD, director of oral medicine services at City of Hope Cancer Center in Duarte, Calif.

Appropriate healing time for dental care prior to treatment is imperative, Epstein adds, because a surgically treated area in the mouth becomes vulnerable to bacteria. Patients with suppressed immune systems can develop infection, which could result in a treatment delay or dose reduction, ultimately affecting the treatment outcome and survival.

Epstein says two weeks of healing time is ideal, but the overall goal is to have the right dental treatment coordinated with medical therapy to avoid those types of risks. Therefore communication between the dentist and oncology team is key.

Dental Care During Treatment
Treating dental issues during cancer therapy is possible but can be difficult and can also lead to complications, such as infection in patients on immunosuppressing chemotherapy and delayed healing of affected oral tissue in patients receiving high-dose radiation.

If dental treatment is needed during a cycled chemotherapy, it must be coordinated between cycles and at a time when white cell counts are high, Epstein says.

For patients receiving radiation for head and neck cancers, the dentist needs to understand the risks for healing and communicate with the oncologist to understand which regions are involved in the radiation fields, Epstein says. The dentist should also be aware of any previous or ongoing bisphosphonate use and understand the associated risks.

“We function as a part of the oncology team for all of our patients,” Abbott says. “I understand the blood work that I get back, and I understand what it is that I need to look for in order to keep the patient safe and then develop my treatment plan around that.”

Preparation and Coordination
A less common but significant oral complication involves bone healing, or lack thereof. Because radiation can damage bone cells, limiting their ability to heal, any future trauma or surgery to irradiated bone can cause osteonecrosis, or bone death.

Bisphosphonates and the RANK ligand inhibitor Xgeva (denosumab)—used to maintain bone density and prevent fractures in people with bone metastases—have also been associated with increased risk for osteonecrosis of the jaw (ONJ), which can occur in 1 to 2 percent of patients on these therapies, according to a 2010 study published in the Journal of Clinical Oncology.

A study published in 2009 in Annals of Oncology showed that preventive dental measures can significantly decrease the risk of developing ONJ. In 2003 and 2004, the FDA updated inserts for the intravenous bisphosphonates Aredia (pamidronate) and Zometa (zoledronic acid) recommending a dental exam with preventive dentistry prior to cancer treatment.

“The main prevention is treatment of the at-risk dental conditions before you’ve had a long-term effect on the bone,” Epstein says. The FDA also warns against invasive dental procedures if possible during or following bisphosphonate use, noting that the majority of reported cases of ONJ have been associated with dental procedures, such as tooth extraction, and many had signs of local infection.

Whether a tooth is extracted from an irradiated area or following bisphosphonate use, Epstein says it must be done carefully. “You want a specialist surgeon to do that with coordination with the cancer center and with people who have supported this need before.”

Therapies Making “A Huge Difference”
After her diagnosis of metastatic renal cell carcinoma in 2009, Linda Morris had two extractions before starting Zometa. When an exposed jaw area wouldn’t heal, she developed osteonecrosis. After visiting six dentists over two years, the 67-year-old saw Abbott.

To prevent infection, Abbott had her apply AO ProVantage twice daily and rinse her mouth with non-alcoholic antibacterial chlorhexidine, as well as clean her teeth with a water flosser. To promote healing, Abbott removed necrotic tissue and performed a comprehensive cleaning every two weeks. For the first time, Morris began to see progress.

“The biggest problem I had was not being able to find the dental care I needed,” Morris says.

“The topically applied gel has made a huge difference in how we can treat this problem,” Abbott says. “We’ve had two cases where the necrotic bone has been totally resolved.”

2011-12-22T15:08:57-07:00December, 2011|Oral Cancer News|

Acupuncture can prevent radiation-induced chronic dry mouth

Author: staff

When given alongside radiation therapy for head and neck cancer, acupuncture has shown for the first time to reduce the debilitating side effect of xerostomia, according to new research from The University of Texas MD Anderson Cancer Center and Fudan University Shanghai Cancer Center.

The study, published in the journal Cancer, reported findings from the first randomised controlled trial of acupuncture for the prevention of xerostomia.

Xerostomia, or severe dry mouth, is characterised by reduced salivary flow, which commonly affects patients receiving radiotherapy for head and neck cancer. Most current treatments are palliative and offer limited benefit, according to Lorenzo Cohen, Ph.D., professor in MD Anderson’s Departments of General Oncology and Behavioral Science and director of the Integrative Medicine Program.

The condition impairs quality of life for patients, as it creates difficulties eating, speaking and sleeping, while also increasing the risk for oral infections.

“There have been a number of small studies examining the benefits of acupuncture after xerostomia develops, but no one previously examined if it could prevent xerostomia,” said Cohen, who is also the study’s principal investigator. “We found incorporating acupuncture alongside radiotherapy diminished the incidence and severity of this side effect.”

Cohen and his colleagues examined 86 patients with nasopharyngeal carcinoma, treated at Fudan University Shanghai Cancer Center. Forty patients were randomised to acupuncture and 46 to the standard of care. Those in the treatment arm received acupuncture therapy three times per week during the seven-week course of radiotherapy. Patients were evaluated before radiotherapy, weekly during radiotherapy, and then again one and six months later.

The results were based on data derived from two self-report questionnaires and measuring actual saliva flow. Patients completed the Xerostomia Questionnaire (XQ), an eight-item survey which assessed symptoms consistent with the condition. XQ scores under 30 corresponded to mild or no symptoms of xerostomia.

The second measure, MD Anderson Symptom Inventory Head and Neck (MDASI-HN), ranked the severity of cancer-related symptoms, other than xerostomia, and their interference with quality of life. The team also measured saliva flow rates using standardised sialometry collection techniques.

Benefits Noticed Quickly

“What was quite remarkable was that we started to see group differences as early as three weeks into radiotherapy for the development of xerostomia, cancer-related symptoms that interfere with quality of life, and saliva flow rates – an important objective measure,” said Zhiqiang Meng, M.D., Ph.D., co-principle investigator of the study and deputy chair of the Department of Integrative Oncology, Fudan University Shanghai Cancer Center.

The largest group differences in XQ scores were seen by the end of radiotherapy, but the differences persisted over time. By one month after the end of radiotherapy, 54.3 percent of the acupuncture group reported XQ scores greater than 30, compared to the control group at 86.1 percent. By six months after radiotherapy, the numbers dropped to 24.1 percent in the acupuncture group and 63.6 percent of the control group still reporting symptoms of xerostomia. Saliva flow rates were also greater in the acupuncture group, starting at three weeks into radiotherapy and persisting through the one and six month follow-up.

Acupuncture also helped cancer-related symptoms, other than xerostomia, as measured by the MDASI-HN questionnaire, with differences that emerged in week three and continued through six months.

“The medical implications are quite profound in terms of quality of life, because while chronic dry mouth may sound benign, it has a significant impact on sleeping, eating and speaking,” Cohen said. “Without saliva, there can be an increase in microbial growth, possible bone infection and irreversible nutritional deficits.”

Additional studies are needed to determine the mechanisms for the benefits of acupuncture, and while the study didn’t examine this issue, Cohen said it may have an impact on local blood flux, specifically at the parotid gland.

Further research is planned, including a large trial conducted at MD Anderson in collaboration with Fudan University Shanghai Cancer Center. Both centers will enroll 150 patients undergoing radiotherapy for head and neck cancer: 50 will receive acupuncture, 50 sham acupuncture and 50 will be enrolled in a control group. Researchers will also examine saliva constituents and a number of other measures to better determine the mechanisms of acupuncture.

Source: MD Andersen Cancer Center: Cancer

2011-11-27T14:18:34-07:00November, 2011|Oral Cancer News|

Proper dental care for cancer patients: why it is important

Author: Alan B. Sheiner DDS

Common side effects from radiation therapy are not stressed enough in dental schools, but they can be managed and even prevented.

A few weeks ago, I was contacted by a retired physician with whom I had not spoken for a number of years since he retired from practice to become a “gentleman farmer” in the country. While I was happy to hear from him, his news was not so good. He was calling because he had been treated for base of tongue cancer and his teeth were “coming apart”. His cancer treatment consisted of chemotherapy and radiation therapy. Unfortunately, he somehow “slipped through the cracks” and his oral cavity was now suffering from some of the side effects of the cancer therapy – fortunately he is currently cancer free.

The oral cavity, one of the most complex and visible organ systems in the body, is invariably compromised as a result of treatment for head and neck cancer. Whether the malignancy is to be treated by surgery, radiation therapy, chemotherapy or a combination of these modalities, the function, if not also the form, of the oral cavity will be impacted. Aside from the obvious physical changes after cancer surgery to the head and neck region, there are issues which usually accompany radiation therapy to the head and neck region.

There may be side effects from cancer therapy, some of which can be devastating, but preventable or manageable with proper precautions and care. The most common side effects for head and neck cancer patients who undergo radiation therapy are:

Dry Mouth (xerostomia)
Post Radiation Tooth Decay
Inability to open the mouth wide (Trismus)
Necrosis of soft tissue and bone (osteoradionecrosis)
Impaired ability to heal from wounds in the oral cavity

Prior to commencement of active treatment, each patient should be thoroughly evaluated by a dentist well versed in the management and care of the irradiated head and neck cancer patient. Unfortunately, this subject has not been stressed in dental school. Even if a dentist has had some instruction, his or her clinical experience might be quite limited. A real life example of this is a lady irradiated for a parotid gland tumor. The parotid gland (we have two) is a major salivary gland. Her general dentist provided her with fluoride applicators, but unfortunately this practitioner did not appreciate the importance of using a neutral pH fluoride gel. The acidulated fluoride gel, normally used when a dentist or hygienist gives a fluoride treatment, literally ate into the surfaces of this woman’s porcelain crowns. Now, in addition to having a dry mouth from radiation, she also has multiple crowns with surfaces like sandpaper. These expensive restorations could not be salvaged and required replacement. In short, the dentist remembered that radiated patients should have daily fluoride treatment. He just did not have a genuine understanding of how to accomplish the task properly.

The most common and profound side effects of irradiation to the head and neck region are: dry mouth (since the major salivary glands are almost always damaged by the therapy), post-irradiation dental caries (a preventable situation), the risk of osteoradionecrosis (non-healing chronic bone death in irradiated bone which has a compromised blood supply) and trismus (an inability to open the mouth fully).

As always, your dentist is the best resource and first person you should see for consultation.

New Guidelines for Reirradiation of Head and Neck Cancer

Source: Medscape News Today

When head and neck cancer recurs and surgery is not an option, reirradiation provides the only potentially curative option. However, because the tumor often recurs in the same place or very close to tissue that has already been irradiated, this treatment approach represents a “significant challenge.”

For this reason, it should be handled at a tertiary-care center, according to a new guideline issued by the American College of Radiology. Specifically, it stipulates that the tertiary center should have a head and neck oncology team that is equipped with the resources and the experience to manage the complexities and toxicities of retreatment.

In the guideline, published in the International Journal of Radiation Oncology, Biology and Physics, a panel of experts outline appropriateness criteria for various clinical scenarios that arise with such patients.

It provides a consensus on how patients should be managed.

“This is an important document because it is the first set of guidelines for the potentially curative treatment of patients who have regrowth of head and neck tumors. It provides a consensus on how patients should be managed,” coauthor Madhur Kumar Garg, MD, said in a statement. Dr. Garg is from the Department of Radiation Oncology at Montefiore Medical Center, in the Bronx, New York, where about a dozen reirradiation procedures are performed annually.

Commitment to Retreatment

Retreatment is justified because clinical trial results have shown that local treatment improves overall survival, the panel of experts notes.

However, they emphasize that, before a commitment to retreatment is made, patients presenting with recurrent or second primary tumors need to undergo careful restaging evaluation. In addition to computed tomography (CT) or magnetic resonance imaging to evaluate the extent of the recurrent tumor, the panel urges that strong consideration be given to positron emission tomography with CT to evaluate for metastatic disease, or “at a minimum, a CT scan of the chest should be performed.”

In addition, a detailed history and assessment is needed, which includes documentation of the sequelae of previous treatment, such as fibrosis, carotid stenosis, dysphagia, xerostomia, and osteoradionecrosis.

Retreatment options include surgical resection and palliative chemotherapy — both are regarded as standard of care, the panel writes. But for patients with unresectable disease, reirradiation is the “only potentially curative treatment,” they add.

Two phase 2 clinical trials conducted by the Radiation Therapy Oncology Group (RTOG) have shown survival outcomes with reirradiation plus chemotherapy that appear to be superior to those seen with chemotherapy alone in other studies. However, “whether this apparent improvement is the result of selection bias is uncertain,” the panel explains. A larger phase 3 comparing reirradiation plus chemotherapy with chemotherapy alone was closed because of poor accrual.

In terms of the dose of radiation delivered in the second treatment course, it appears that at least 50 to 60 Gy is needed, the experts report. Both of the phase 2 studies conducted by the RTOG delivered a total dose of 60 Gy, using an accelerated hyperfractionated regimen delivering 1.4 Gy twice daily in 4 week-on/week-off cycles. Multiple single-institution reports of reirradiation have used once-daily standard fractionation in a planned continuous treatment course with less toxicity, they note. However, differences in study designs and in the chemotherapy regimens make it difficult to discern what independent effect, if any, differences in radiation fractionation had on the toxicity that was seen.

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

Palifermin Decreases Severe Oral Mucositis of Patients Undergoing Postoperative Radiochemotherapy for Head and Neck Cancer: A Randomized, Placebo-Controlled Trial



This randomized, placebo-controlled trial found that weekly palifermin was associated with decreased incidence and duration of severe oral mucositis in patients undergoing postoperative chemoradiotherapy for head and neck cancer.


OncologySTAT Editorial Team

Combined chemoradiotherapy (CRT) offers improved outcomes after resection of locally advanced head and neck cancer but also increases the risk of oral mucositis, a debilitating and potentially dose-limiting toxicity of locoregional treatment. Palifermin, an analogue of keratinocyte growth factor, is FDA approved to prevent and treat mucositis in patients undergoing high-dose myelotoxic therapy for hematologic malignancies. In this multicenter, randomized, placebo-controlled trial, Henke et al evaluated whether palifermin reduces severe oral mucositis in patients undergoing CRT after surgical resection of locally advanced head and neck cancer.

Adult patients receiving postoperative CRT for high-risk stage II to IVB head and neck squamous cell carcinoma and with an ECOG performance status of 0 to 2 were enrolled from 38 centers in Europe, Australia, and Canada. Eligible study patients were stratified by tumor location (oral cavity/oropharynx or hypopharynx/larynx) and residual tumor (R0 [complete resection] or R1 [incomplete resection]). Study patients received a radiation dose of 60 Gy (R0 group) or 66 Gy (R1 group) plus cisplatin 100 mg/m2 on days 1 and 22, with the study drug administered 3 days prior to starting CRT and then weekly for 6 weeks. Patients who underwent radiotherapy after 6 weeks received an additional 100 mg/m2 of cisplatin and study drug. Oral saline rinses, topical anesthetics, feeding tubes, and hematopoietic growth factors were permitted; oral anti-inflammatory, antifungal, or antibiotic solutions were not permitted.

Patients initially were randomized to three treatment arms: weekly palifermin 180 µg/kg throughout CRT, weekly palifermin 180 µg/kg for 4 doses followed by weekly placebo through the remainder of CRT, or weekly placebo throughout CRT. However, adverse event monitoring led to a restart of the study after enrollment of the first 17 patients, with subsequently enrolled patients randomized to receive weekly palifermin 120 µg/kg (n = 92) or weekly placebo (n = 94) throughout CRT (for a minimum of 7 weeks); efficacy analyses were based on these 186 patients. The primary endpoint was the incidence of severe oral mucositis (WHO grade 3 or 4). Oral mucosa assessments occurred twice weekly throughout CRT and until resolution of oral mucositis to WHO grade ≤ 2 or week 15, whichever occurred first. Among secondary endpoints were duration of and time to onset of severe oral mucositis, incidence of grade ≥ 2 xerostomia at month 4, and incidence of treatment breaks (≥ 5 missed consecutive radiation fractions; chemotherapy delays or discontinuation). Time to disease progression and overall survival (OS) also were assessed.

Of 186 patients randomized to weekly palifermin 120 µg/kg or placebo, 79 in the palifermin arm (86%) and 82 in the placebo arm (87%) completed all oral evaluations. Patients in the palifermin group received a mean radiation dose of 59.7 Gy in a mean of 43.5 days and a mean cumulative cisplatin dose of 217.1 mg/m2. Patients in the placebo group received a mean radiation dose of 59.8 Gy in a mean of 43.2 days and a mean cumulative cisplatin dose of 206.4 mg/m2. Severe oral mucositis was observed in 47 patients (51%) in the palifermin group and 63 patients (67%) in the placebo group (P = .027). The median duration of severe oral mucositis was 4.5 days in the palifermin group vs 22.0 days in the placebo group (P = .037), and the median time to develop severe oral mucositis was 45 vs 32 days (P = .022), respectively. Incidence of grade ≥ 2 xerostomia at month 4, incidence of treatment breaks, time to disease progression, and OS did not differ significantly between the two groups.

In conclusion, weekly palifermin at a dose of 120 µg/kg was associated with reduced incidence, increased time to development, and decreased duration of severe oral mucositis in patients undergoing postoperative CRT for locally advanced head and neck cancer. However, differences in other efficacy endpoints were not statistically different in patients receiving palifermin. Further study of palifermin in this patient population is needed.

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

2011-09-20T10:21:43-07:00September, 2011|Oral Cancer News|

Cannabis use and oral diseases


Questions: What is the effect of cannabis usage on the oral environment?

Data sources
Medline and the Cochrane Central register of controlled trails (CENTRAL).

Study selection
Randomised Controlled Trials, Controlled Clinical Trials and Cohort Studies conducted on humans investigating cannabis usage were included. Screening was performed independently by two reviewers. Only English language studies were included. Case reports, letters and historical reviews were excluded.

Data extraction and synthesis
A narrative synthesis was conducted.

Seven studies were included and a range of cannabis-associated oral side effects identified.

Based on the limited data, it seems justified to conclude that with increasing prevalence of cannabis use, oral health care providers should be aware of cannabis-associated oral side effects such as xerostomia, leukoedema and an increased prevalence and density of Candida albicans.

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

U of A study finds ways to help end dry mouth in cancer patients

Source: e! Science News

For patients suffering from cancer in the mouth or throat, a recent study shows that a treatment called submandibular gland transfer will assist in preventing a radiation-induced condition called xerostomia. Also known as dry mouth, xerostomia occurs when salivary glands stop working. University of Alberta researcher Jana Rieger likens the feeling of xerostomia to the experience of the after-effects of having surgery and anesthetic—but the feeling is permanent.

While the importance of healthy saliva glands may be an afterthought for some patients when battling cancer, the long-lasting effects create a number of problems for them when they are in remission.

“We need saliva to keep our mouths healthy,” said Rieger. “Without saliva, people can lose their teeth, dentures don’t fit properly and the ability to swallow and speak is severely altered.”

The study conducted by Rieger, a speech language pathologist in the Faculty of Rehabilitation Medicine, looked at functional outcomes—speech changes, swallowing habits and the quality of life of patients with mouth and throat cancers—as they received two different types of treatments prior to and during radiation.

The first group of patients underwent the submandibular gland transfer. This method was pioneered by Hadi Seikaly and Naresh Jha at the University of Alberta in 1999. The transfer involves moving the saliva gland from under the angle of the jaw to under to the chin. Prior to this procedure, the saliva gland was in line for the radiation. Seikaly says, “Most patients, when they are cured from cancer, complain of one major thing: dry mouth.”

The second group in the study took the oral drug salagen. Rieger says, “Studies have shown in the past that if this drug was taken during radiation, it might protect the cells in the salivary glands.”

According to the study findings, both groups had the same results in terms of being able to speak properly but where the main difference was in swallowing. The group taking the drug had more difficulty.

Rieger said, “This group needed to swallow more, and it took a longer time to get food completely out of their mouth and into the esophagus. Because they had trouble eating, they may become nutritionally comprised.”

This leads to a host of other problems. Dry mouth causes one to drink large volumes of water, which leads to numerous trips to the bathroom. Difficulty swallowing causes issues with eating food while it’s still hot and it takes the patients a long time to complete a meal.

As a result of these problems, Rieger found the quality life for most patients decreased significantly. “People suffering from xerostomia no longer want to go out eat and be in social settings. Consuming water to quench dry mouth means they have difficulty in getting a good night’s sleep. Some become depressed and avoid going out.”

Based on this study, the authors hope to encourage patients to have the submandiublar gland transfer as a preventative treatment for xerostomia prior to radiation for mouth and throat cancers.


Reirradiation with intensity-modulated radiotherapy in recurrent head and neck cancer.

Source: HighWire- Stanford University

In this retrospective investigation we analyzed outcome and toxicity after intensity-modulated reirradiation of recurrent head and neck cancer. METHODS: Thirty-eight patients with local recurrent head and neck cancer were evaluated. The median dose of initial radiotherapy was 61 Gy. Reirradiation was carried out with step-and-shoot intensity-modulated radiotherapy (median dose: 49 Gy). RESULTS: Median overall survival was 17 months, and the 1- and 2-year overall survival rates were 63% and 34%. The 1- and 2-year local control rates were 57% and 53%. Distant spread occurred in 34%, and reirradiation induced considerable late toxicity in 21% of the patients. Thirty-two percent showed increased xerostomia after reirradiation. The risk for xerostomia was significantly higher for cumulative mean doses of ?45 Gy to parotid glands. Considering median cumulative maximum doses of 53 Gy to the spinal cord and 63 Gy to the brainstem, no late toxicities were observed. CONCLUSIONS: Reirradiation with intensity-modulated radiotherapy in recurrent head and neck cancer is feasible with acceptable toxicity and yields encouraging rates of local control and overall survival.

� 2011 Wiley Periodicals, Inc. Head Neck, 2011.

2011-02-09T11:45:36-07:00February, 2011|Oral Cancer News|
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