Patients undergoing radioactive iodine (RAI) treatment for thyroid cancer are at an increased risk of developing sialadenitis, which is likely to interfere with their quality of life (QOL), according to a study in Otolaryngology Head and Neck Surgery (2013;148:746–752).
“We found out that, in general, sialadenitis is an underreported disorder,” said the study's lead author, M. Boyd Gillespie, MD, MSc, Professor of Medicine in the Department of Otolaryngology–Head and Neck Surgery at Medical University of South Carolina (MUSC). “It's also not well recognized by clinicians who treat thyroid cancer. Therapies are available, though, so raising awareness among treating physicians and patients is important.”
This study allows oncologists to better stratify risk for a potentially serious side effect of this therapy, said Craig Stevens, MD, PhD, Chair of Radiation Oncology for Beaumont Health System in Michigan. “A lot of what we do is getting appropriate informed consent. Having information about the risk after undergoing RAI helps oncologists to better inform patients about this side effect and to proactively manage it.”
Additionally, recognizing the significant impact of sialadenitis on quality of life in thyroid cancer patients is critical to their care, said Rohan R. Walvekar, MD, Associate Professor in the Department of Otolaryngology–Head & Neck Surgery, Director of the Head & Neck Service at MCLANO & Earl K. Long Hospitals, and Director of Clinical Research & Salivary Endoscopy Service at Louisiana State University School of Medicine.
“I've seen patients who become miserable over a period of time as their glands become fibrotic. They develop dry mouth and can't eat properly.”
Gillespie and his colleagues conducted a retrospective, self-administered questionnaire study of 121 women and 24 men, with a mean age of 52, treated for thyroid cancer at MUSC Hollings Cancer Center. Three patients were excluded because RAI history was not available. Sixty-eight percent of patients had papillary carcinoma and 23 percent had a follicular variant of papillary carcinoma; the remaining diagnoses included follicular, oxyphilic, and Hürthle cell cancer.
Salivary gland problems were reported by about 12 percent of patients who received low-dose RAI of 0 to 150 mCi (84 patients) and about 24 percent of those receiving high-dose RAI of greater than 150 mCi (58 patients).
Sialadenitis was 2.47 times more likely to occur in those who received RAI of greater than 150 mCi compared with those who received 1 to 150 mCi.
When compared with patients who received 0 to 150 mCi, those who received more than 150 mCi had a significant decline in the University of Washington Quality of Life Questionnaire (UW-QOL) recreation domain (74.07 vs. 83.73) and the MD Anderson Dysphagia Inventory (MDADI) general swallowing domain (79.65 vs. 97.90).
The higher dose also resulted in a significant reduction in the Xerostomia-Related Quality of Life (XeQOLS) domains of pain (6.88 vs. 5.73), personal/psychological functioning (6.86 vs. 5.71), and social functioning (4.19 vs. 3.5).
In an analysis omitting patients who did not receive RAI and comparing exposure of 1 to 150 mCi to doses greater than 150 mCi, the higher dose was associated with a significant reduction in the UW-QOL recreation domain (74.07 vs. 83.19) and the MDADI daily activities domain (79.65 vs. 89.64).
There was a trend for lower QOL on XeQOLS domains. However, when the results were stratified by the presence of sialadenitis, physical functioning, psychological/personal, pain, and social domains were all significantly lower in the group receiving more than 150 mCi.
The main risk factor for developing sialadenitis is the total RAI dose, Gillespie said. “The tipping point for symptoms is once the patient has been exposed to over 150 mCi. Although iodine is taken up by thyroid tissue, it's also taken up by salivary glands.”
Based on the study, whether RAI is indicated should be carefully considered because the treatment is not without consequence, said Amy Y. Chen, MD, MPH, Professor in the Department of Otolaryngology and Head and Neck Surgery and Professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine. “In addition, we should use caution in the amount of RAI we administer since it appears to be a dose-response curve.”
While RAI is used in many cases of papillary and follicular cancer, oncologists have become more selective about recommending this adjuvant therapy based on the data attesting to its efficacy, noted Douglas Frank, MD, Director of Head and Neck Surgical Oncology at North Shore LIJ Cancer Institute and Co-director of the Center for Head and Neck Oncology at New York Head and Neck Institute. “This is primarily because we know that RAI is not beneficial to all who receive it, particularly younger patients with early-stage disease.”
Physicians should also keep in mind patients who are particularly at risk for sialadenitis, including those with autoimmune conditions such as Sjögren's syndrome, salivary gland infections, juvenile recurrent parotitis, or diabetes, Walvekar said. Also at higher risk are older patients who may have poor oral hygiene and individuals with salivary gland stones.
Prevention and Treatment
Gillespie noted that prevention of sialadenitis is not standardized. “For now, patients are told to drink plenty of water and to suck on solid sour candies to help with clearing the salivary glands of any radioactive material.”
Some controversy exists over when patients should start using sour candy in the course of treatment. “Because sucking on something sour, which increases blood flow to the salivary gland and the gland's activity, may increase uptake of radiation, you want to time using the candy for after RAI has occurred to help empty out the radioactive material.”
For patients who have their first episode of sialadenitis, physicians should recommend increased hydration, sour candies, vitamin C drops, mucous thinning agents, and anti-inflammatory drugs, as well as steroids in severe cases, he said.
Walvekar added that traditional management of the condition may also include salivary gland massage.
Another potential treatment option for sialadenitis is salivary endoscopy, which involves inserting a scope into the natural drainable pathway of the salivary glands and into the ducts where the practitioner tries to identify any scar tissue or blockages of the ductal system, Gillespie explained. The use of microinstruments, as well as irrigation and flushing with saline, can help rid the area of debris. Additionally, the application of antibiotics can be used to reduce infections, while steroids can help decrease inflammation of the glands.
An endoscopic assessment of the ducts, followed by salivary gland washout with saline and steroids, is a viable option, although there is not evidence to support having every patient undergo the procedure after RAI, Walvekar said.
“We don't know the true effect of the intervention. We generally see patients at the worst end of it, so they tend to experience a benefit. How long this benefit lasts also needs to be assessed. However, the procedure itself is so low risk that it's almost worth to have it than not.”
Walvekar also noted that most of the published research on salivary endoscopy for RAI-related sialadenitis involves small case series of 10 to 20 patients at various centers around the country. Overall, as reported in the available literature, about 75 percent of those treated reported a significant improvement in symptoms.
Generally, patients who are good candidates for salivary endoscopy are those who have three episodes of sialadenitis within six months or four or more in the course of a year, he added.
Patients who have stenosis of the salivary glands may benefit from endoscopic dilation of the glands with a stent, said Walvekar, who is an inventor of such a device. These stents usually stay in place for two to four weeks and can be removed in the office.
Stents are beneficial in certain patients, said Gillespie. If scar tissue or blockage occurs in larger salivary ducts, then stents can sometimes be helpful by opening up the tissue and allowing it to heal, but they are not always needed.
Stevens said that whatever the treatment for salivary morbidity, oncologists with experience managing such side effects should be involved. Cancer therapies can result in side effects that are often quite significant to the patient but not to the general observer, he said.
Frank said physicians probably don't talk enough about RAI side effects with patients. Individuals with thyroid cancer are treated by a multidisciplinary team, which means that its members may be assuming that someone else is providing counseling about salivary morbidity, he explained.
To compound the problem, patients often don't think about reporting salivary gland problems because they are dealing with a cancer diagnosis, Walvekar said.
Physicians should be telling patients that short-term side effects of RAI are common and include salivary gland swelling, discomfort, and change in taste, said Frank. These side effects most often subside once the RAI washes out of the excretory glands. Recurrent salivary gland inflammation is rare but does occur.
Patients should also be told that their risk of sialadenitis increases as their exposure to RAI increases, Gillespie said.
In addition to being educated about the usual measures to help prevent and manage the condition, patients should be encouraged to talk with their physicians about salivary endoscopy and washout if they experience any morbidity, Walvekar added.
“It may not seem very important at the time, but the procedure could be life changing. I've seen patients who ignore their symptoms over time and eventually become so uncomfortable that they ask to have their salivary glands removed. I'm not promoting that all patients undergo salivary endoscopy, but they should know their options.”