Introduction
Xerostomia is one of the most common toxicities of chemoradiation in the treatment of head and neck cancer, and is primarily a result of radiation-induced damage to the parotid glands. Because xerostomia can eventually lead to a range of issues starting with acute mucositis and increased risk of oral candidiasis, to dental caries, painful denture fitting, speech and even changes in taste perception, there is an undeniable bearing on the quality of life.Reference Bruce1, Reference Warde, O’Sullivan and Aslanidis2 Current treatments with pharmacologic sialogogues such as oral pilocarpine or saliva substitutes have been shown to provide some temporary relief however these may also cause intolerable cholinergic side effects.Reference Warde, O’Sullivan and Aslanidis2, Reference Wong, Jones, Sagar, Babjak and Whelan3
Saliva serves multiple roles including protection, taste sensation, buffering, digestion, mineralisation, lubrication and tissue coating.Reference Jensen, Pedersen, Reibel and Nauntofte4, Reference Nauntofte, Tenovuo and Lagerlöf5 Typically, the magnitude of reduction of salivary production is related to the radiation dosage and the volume of salivary gland tissue in the treatment field with significant decrease in flow of saliva seen within the first few days of treatment with an average nadir of 3 weeks.Reference Wong, Deshmukh and Wyatt6 The duration of radiation-induced xerostomia is controversial, with variable evidence for partial recovery.Reference Eisbruch, Kim, Terrell, Marsh, Dawson and Ship7
Studies involving acupuncture-like transcutaneous nerve stimulation (ALTENS) have had promising results suggesting durably improved saliva production, without many of the side effects of standard pharmacologic treatment.Reference Wong, Jones, Sagar, Babjak and Whelan3, Reference Wong, Deshmukh and Wyatt6, Reference Wong, James and Sagar8 Both the single institution and multi-institution reports have showed benefit in patients ranging from 3 to 27 months from the time of completion of chemoradiation therapy to beginning ALTENS therapy.Reference Wong, Jones, Sagar, Babjak and Whelan3, Reference Wong, Deshmukh and Wyatt6, Reference Wong, James and Sagar8 ALTENS in patients further removed from completion of radiation therapy has not previously been reported.
Clinical History
A 69-year-old male with history of T2N2 base of tongue cancer underwent definitive treatment with concurrent cisplatin and external beam radiation therapy as previously described and completed on 8 December 2009.Reference Mix9 The patient tolerated treatment relatively well; however, soon after completing treatment, he endorsed moderate xerostomia requiring him to carry around a water bottle and frequently use ice chips, which only temporarily palliated daily symptoms. In 2010, the patient was enrolled on RTOG 0537 and randomised to receive pilocarpine.Reference Wong, Deshmukh and Wyatt6 This therapy did not appreciably improve his xerostomia. Xerostomia did not improve over the next 5·5 years of follow-up.
Recently our department made ALTENS available to all patients without charge. This patient was offered ALTENS therapy and completed one round of twice weekly for 12 weeks/RTOG 0537.Reference Wong, James and Sagar8 Following this course, the patient reported continued xerostomia without significant improvement. At the patient’s request to ‘try something else’, a second round of ALTENS was decided upon. After 20 treatments in the second round, he reported that he would not be continuing because his xerostomia had resolved, and he now was having ‘drooling’. One year later, the patient has maintained his abundant saliva production and it was noted that he has not had any changes to his chronic medications in the last 2-year interval.
Discussion
In a single institution, phase II trial, Wong et al.,Reference Wong, Jones, Sagar, Babjak and Whelan3 demonstrated that ALTENS was able to improve saliva production with improvement in xerostomia symptoms that were sustained for at least 6 months after completion of the ALTENS therapy with patients no more than 27 months from initial radiation therapy.Reference Wong, Jones, Sagar, Babjak and Whelan3 The cooperative multi-centre phase II study that followed, RTOG 0537, limited eligibility to patients who had completed radiation therapy greater than 3 months but less than 2 years previously.Reference Wong, Deshmukh and Wyatt6, Reference Wong, James and Sagar8 Thus, there have been no current or previous studies evaluating potential benefits of ALTENS therapy for patients with long-standing symptoms greater than 2 years.
RTOG 0537 established an ALTENS regimen of twice weekly, 20-minute sessions for 12 weeks. ALTENS efficacy was evaluated using the self-reported University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS) given at baseline and at 6 months after treatment.Reference Henson10 In the phase II results, positive treatment response was seen in 86% of patients, with a median percent of XeQOLS score reduction of 42·9%, and no significant associated acute side effects.Reference Wong, James and Sagar8 The recently published phase III results showed ALTENS was at least equivalent to pilocarpine in the percent of XeQOLS score reduction and had a higher proportion of positive responders at 15 months (83 and 63%, respectively; p=0·04).Reference Wong, Deshmukh and Wyatt6 In addition, there was significantly less grade 3 or less adverse events seen in the ALTENS group (20·8% of the ALTENS group versus 61·6% of the pilocarpine).Reference Wong, Deshmukh and Wyatt6
Given these phase III findings and the current report, it may be of interest to consider studying the efficacy of ALTENS therapy in the treatment of radiation-induced xerostomia for patients that have had a lengthy duration since the end of their radiation treatment. Though we have no formal measures of xerostomia in this patient, his ability to produce and maintain enough saliva to drool requires no advanced metrics to be impressive. The potential of offering such a therapy to those patients seen routinely in follow-up at 3 years, 5 years and beyond might benefit a long-suffering population.
Conclusion
ALTENS has been shown to be effective in the reduction of symptoms of xerostomia secondary to radiation therapy, however, this has only been observed in patients that completed radiation less than 27 months previously. Our findings offer a promising potential benefit for those longer suffering patients with radiation-induced xerostomia.
Acknowledgement
The authors thank Tabatha McCabe, LPN, for her dedication to applying the ALTENS treatment with diligence and continued compassion for all of her patients.
