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Surgical prevention and management of radiation-induced xerostomia in head-and-neck cancer patients

Sukhia, Rashna H; Sukhia, Hoshang R; Ghandhi, Dinaz

doi: 10.4103/ijssr.ijssr_5_18
Review Article
Free
SDC

Head-and-neck cancer is the sixth most commonly diagnosed cancer in the world and amounts to nearly 3% of all malignancies. Therapeutic irradiation is a common mode of treatment either alone or in conjunction with surgery for treatment of head-and-neck cancers which leads to irradiation-induced xerostomia which may in turn lead to disturbances in taste, speech, and prosthesis wear, etc. Xerostomia may also lead to infections in the oral cavity and rampant carious lesion in teeth. Salivary gland transfer is a surgical procedure done to prevent the gland from radiation exposure during radiotherapy of the head-and-neck region. Management of xerostomia is usually done with systemic or topical pilocarpine or cevimeline, artificial saliva compounds, herbal compounds, acupuncture and acupuncture-like transcutaneous nerve stimulation, low-level laser therapy, etc. with varying effectiveness.

Section of Dentistry (Orthodontics) Department of Surgery, The Aga Khan University and Hospital, Karachi, Pakistan

Deaprtment of Orthodontics, Sir Syed College of Medical Sciences, Karachi, Pakistan

Department of Oral and Maxillofacial Surgery, Altamash Institute of Dental Medicine, Karachi, Pakistan

Address for correspondence:Rashna Sukhia, Section of Dentistry (Orthodontics) Department of Surgery, The Aga Khan University and Hospital, Karachi, Pakistan rashna.aga@aku.edu

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Introduction

Head-and-neck cancer is the sixth most commonly diagnosed cancer in the world and amounts to nearly three percent of all malignancies. 1 , 2 Various surgical, chemotherapeutic, and radiation therapy modalities are utilized for the management of head-and-neck cancer depending on the stage of tumor. Therapeutic irradiation is a common mode of treatment either alone or in conjunction with surgery for treatment of head-and-neck cancers. This irradiation leads to profound xerostomia which may in turn lead to disturbances in taste, speech, and prosthesis wear, etc. Xerostomia may also lead to infections in the oral cavity and rampant carious lesion in teeth. 3

Management of xerostomia is usually done with systemic or topical pilocarpine or cevimeline, artificial saliva compounds, herbal compounds, acupuncture and acupuncture-like transcutaneous nerve stimulation, low-level laser therapy, etc. with varying effectiveness. However, since prevention is better than cure, a surgical procedure called salivary gland transfer is done to prevent the gland from radiation exposure during radiotherapy of the head-and-neck region. This procedure was introduced in 2000 whereby one submandibular gland, which lies contralateral to the location of tumor, is transferred to the submental region under the belly of digastric muscle before beginning radiation therapy. This results in exposure of this gland to only about 5% of the radiation exposure during radiation therapy thus preventing xerostomia from occurring. 4 This article therefore aims to review the literature regarding the surgical prevention and various other modes of management of radiation-induced xerostomia in head-and-neck cancer patients.

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Methods

Literature review using the search terms “head-and-neck cancer and irradiation and surgery and management” was conducted on PubMed, Cochrane library, and EBSCO databases. Last search was conducted on May 27, 2017. Inclusion criteria were peer-reviewed articles, English language, and randomized controlled trials.

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Results and Discussion

Surgical prevention of xerostomia

Salivary gland transfer

Salivary flow rates were significantly reduced in the control group as compared to the salivary gland transfer patients, and it was also observed that the salivary gland transfer patients were better able to regain the salivary flow rate after completion of radiotherapy as compared to the control group. Unstimulated salivary flow rates were 79% compared to their baseline value in salivary gland transfer group and 28% of presurgical values on the control group. Stimulated salivary flow rates also depicted a similar trend with 74% in salivary gland transfer group and 17% in the control group. Patients' perception of loss of saliva was also assessed and only about 11.2% of patients undergoing salivary gland transfer procedure reported moderate/severe or complete loss of saliva amount over 12–18 months after irradiation treatment. Salivary consistency is also affected by irradiation of the salivary glands. Saliva consistency was reported to be “moderately/extremely thick” in 11%–21% of patients undergoing salivary gland transfer procedure; however, salivary consistency did not show a clear association with salivary flow rate. 1 Jha et al. 5 compared the effectiveness of salivary transfer procedure with pilocarpine and concluded that submandibular salivary gland transfer procedure is superior to pilocarpine in the management of radiation-induced xerostomia.

The complications associated with salivary gland transfer procedure include ipsilateral facial edema (13.6%), followed by neck numbness (6.8%). Bleeding/hematoma formation, shoulder weakness, ipsilateral neck numbness, and wound infection all occurred 4.5% of the time. Lingual nerve injury, hypoglossal nerve injury, cerebral embolism/cerebrovascular accident, and gland positional movement occurred 2.5% of the time. 6

Marzouki et al. 7 modified the salivary gland transfer procedure by moving the gland to the parotid region and reported that the procedure was feasible, surgically and oncologically viable, and did not interfere with the radiation therapy.

Management of xerostomia

Systemic or topical pilocarpine

Systemic pilocarpine use has been found to be an effective and well-tolerated modality of treating xerostomia in oral cancer patients undergoing radiotherapy. 8 , 9 Adverse effects reported with the use of pilocarpine include nausea, vomiting, and mild headache. Chitapanarux et al. 10 reported a significant improvement in the xerostomia score after the first 4 weeks of oral pilocarpine administration. Johnson et al. 8 reported an increase in the saliva production; however, it did not correlate with symptom relief in their study. However, LeVeque et al. 9 reported a significant improvement in symptoms following treatment for 8–12 weeks with a dose of 2.5 mg thrice daily. Taweechaisupapong et al. 11 reported that use of 5 mg pilocarpine lozenge was significantly more effective in increasing the salivary flow and decreasing the xerostomia symptoms in head-and-neck cancer patients treated with radiotherapy, as compared to systemic pilocarpine and 3 mg pilocarpine lozenge.

Systemic or topical cevimeline

Cevimeline is another drug used for management of symptoms associated with radiation-induced xerostomia. Chambers et al. 12 , 13 studied the effects of cevimeline hydrochloride 45 mg thrice daily over 52 weeks and reported a significant improvement in xerostomia in 59.2% of their study participants. Adverse effects reported with this drug were excessive sweating, nausea, diarrhea, and dyspepsia. Witsel et al. 14 studied the effect of cevimeline 30 mg three times daily for 6 weeks in patients undergoing head-and-neck radiotherapy in a randomized double-blind placebo-controlled study. They reported no significant difference in the oral health-related quality of life in the two groups and concluded that the role of oral parasympathetic muscarinic secretagogues remains unclear in improving symptoms associated with radiation-induced xerostomia.

Artificial saliva compounds

Davies and Singer 15 in a prospective randomized crossover study using mucin-based artificial saliva and pilocarpine mouthwash (5 mg) three times a day reported a significantly greater relief in symptoms in the pilocarpine mouthwash group as compared to the artificial saliva group. Biotene-containing toothpastes, oral balanced gel, and lactoperoxidase gels have been tested in the literature and have been found useful in improving symptoms associated with xerostomia based on their lubricant properties. 3 , 16 , 17 Momm et al. 18 tested four saliva substitute compounds including gel, carmellose spray, oil, and mucin spray in a prospective crossover study and reported a significant improvement in xerostomia from the baseline. They however recommend that the salivary substitute products may be chosen by the patients based on their comfort with each product. Jellema et al. 19 conducted a pilot study to test the efficacy of Xialine, a xanthan gum-based salivary substitute on xerostomia induced by radiotherapy and found similar results in both the Xialine as well as placebo group. However, speech and senses were reported to be improved in the Xialine group as compared to the placebo group.

Acupuncture and acupuncture-like transcutaneous nerve stimulation

Acupuncture and acupuncture-like transcutaneous nerve stimulation method (codetron) without invasive needles has been used to treat xerostomia induced by radiotherapy in head-and-neck region with promising results. 20 , 21 , 22 , 23 , 24 Wong et al. 22 concluded that the effects of codetron in improving xerostomia were sustained for at least 6 months after therapy. Simcock et al. 23 also reported an improvement in the xerostomia symptoms in group acupuncture-treated patients as compared to group oral care education sessions in patients undergoing radiation therapy for head-and-neck cancer. Wong et al. 24 also carried out a multicenter randomized study to compare the effectiveness of acupuncture-like transcutaneous nerve stimulation device with pilocarpine in patients suffering from radiation-induced xerostomia. They reported no significant difference in the primary endpoint which was change in radiation-induced xerostomia symptom burden in both the groups; however, the acupuncture-like transcutaneous nerve stimulation group reported less adverse effects. Saleh et al. 25 tested the efficacy of low-level laser therapy in a pilot study on patients suffering from radiation-induced xerostomia. They however could not find a significant increase in the salivary flow rate or improvement in xerostomia with the low-level laser therapy. This according to them might be due to fibrosis and acinar atrophy of the glandular structures due to radiation therapy.

Humidifiers

Criswell and Sinha 26 conducted a randomized, controlled crossover pilot study to compare the efficacy of humidifier as compared to a supersaturated humidifier through a nasal cannula in patients suffering from xerostomia induced by radiation therapy in head-and-neck cancer patients. No significant difference was seen in the physical examination scores as well as the patient-reported questionnaire among the two groups. They therefore concluded that supersaturated humidifier had minimal or no additional relief from radiation-induced xerostomia in head-and-neck cancer patients.

Herbal compounds

Ameri et al. 27 assessed the efficacy of a herbal compound containing Malva sylvestris and Alcea digitata as compared to artificial saliva in head-and-neck cancer patients. The grade of dry mouth significantly improved in the herbal compound group as compared to the artificial saliva group, and therefore, the authors support the herbal compound over artificial saliva in reducing symptoms associated with xerostomia induced by radiotherapy in head-and-neck cancer patients.

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Conclusion

It is therefore concluded from the review that surgical prevention of radiation-induced xerostomia in head-and-neck cancer patients with salivary gland transfer procedure may reduce the chance of radiation-induced xerostomia in these patients. Radiation-induced xerostomia after occurrence may be treated with systemic or topical pilocarpine, systemic or topical cevimeline, artificial saliva compounds, acupuncture or acupuncture-like transcutaneous nerve stimulation, low-level laser therapy, humidifiers, and herbal compounds.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

1. Sood AJ, Fox NF, O'Connell BP, Lovelace TL, Nguyen SA, Sharma AK, et al Salivary gland transfer to prevent radiation-induced xerostomia: A systematic review and meta-analysis Oral Oncol. 2014;50:77–83
2. Mercadante V, Al Hamad A, Lodi G, Porter S, Fedele S. Interventions for the management of radiotherapy-induced xerostomia and hyposalivation: A systematic review and meta-analysis Oral Oncol. 2017;66:64–74
3. Epstein JB, Emerton S, Le ND, Stevenson-Moore P. A double-blind crossover trial of oral balance gel and biotene toothpaste versus placebo in patients with xerostomia following radiation therapy Oral Oncol. 1999;35:132–7
4. Jha N, Seikaly H, McGaw T, Coulter L. Submandibular salivary gland transfer prevents radiation-induced xerostomia Int J Radiat Oncol Biol Phys. 2000;46:7–11
5. Jha N, Seikaly H, Harris J, Williams D, Sultanem K, Hier M, et al Phase III randomized study: Oral pilocarpine versus submandibular salivary gland transfer protocol for the management of radiation-induced xerostomia Head Neck. 2009;31:234–43
6. Jha N, Harris J, Seikaly H, Jacobs JR, McEwan AJ, Robbins KT, et al Aphase II study of submandibular gland transfer prior to radiation for prevention of radiation-induced xerostomia in head-and-neck cancer (RTOG 0244) Int J Radiat Oncol Biol Phys. 2012;84:437–42
7. Marzouki HZ, Elkhalidy Y, Jha N, Scrimger R, Debenham BJ, Harris JR, et al Modification of the submandibular gland transfer procedure Laryngoscope. 2016;126:2492–6
8. Johnson JT, Ferretti GA, Nethery WJ, Valdez IH, Fox PC, Ng D, et al Oral pilocarpine for post-irradiation xerostomia in patients with head and neck cancer N Engl J Med. 1993;329:390–5
9. LeVeque FG, Montgomery M, Potter D, Zimmer MB, Rieke JW, Steiger BW, et al Amulticenter, randomized, double-blind, placebo-controlled, dose-titration study of oral pilocarpine for treatment of radiation-induced xerostomia in head and neck cancer patients J Clin Oncol. 1993;11:1124–31
10. Chitapanarux I, Kamnerdsupaphon P, Tharavichitkul E, Sumitsawan Y, Sittitrai P, Pattarasakulchai T, et al Effect of oral pilocarpine on post-irradiation xerostomia in head and neck cancer patients: A single-center, single-blind clinical trial J Med Assoc Thai. 2008;91:1410–5
11. Taweechaisupapong S, Pesee M, Aromdee C, Laopaiboon M, Khunkitti W. Efficacy of pilocarpine lozenge for post-radiation xerostomia in patients with head and neck cancer Aust Dent J. 2006;51:333–7
12. Chambers MS, Jones CU, Biel MA, Weber RS, Hodge KM, Chen Y, et al Open-label, long-term safety study of cevimeline in the treatment of postirradiation xerostomia Int J Radiat Oncol Biol Phys. 2007;69:1369–76
13. Chambers MS, Posner M, Jones CU, Biel MA, Hodge KM, Vitti R, et al Cevimeline for the treatment of postirradiation xerostomia in patients with head and neck cancer Int J Radiat Oncol Biol Phys. 2007;68:1102–9
14. Witsell DL, Stinnett S, Chambers MS. Effectiveness of cevimeline to improve oral health in patients with postradiation xerostomia Head Neck. 2012;34:1136–42
15. Davies AN, Singer J. A comparison of artificial saliva and pilocarpine in radiation-induced xerostomia J Laryngol Otol. 1994;108:663–5
16. Nagy K, Urban E, Fazekas O, Thurzo L, Nagy E. Controlled study of lactoperoxidase gel on oral flora and saliva in irradiated patients with oral cancer J Craniofac Surg. 2007;18:1157–64
17. McMillan AS, Tsang CS, Wong MC, Kam AY. Efficacy of a novel lubricating system in the management of radiotherapy-related xerostomia Oral Oncol. 2006;42:842–8
18. Momm F, Volegova-Neher NJ, Schulte-Mönting J, Guttenberger R. Different saliva substitutes for treatment of xerostomia following radiotherapy.A prospective crossover study Strahlenther Onkol. 2005;181:231–6
19. Jellema AP, Langendijk H, Bergenhenegouwen L, van der Reijden W, Leemans R, Smeele L, et al The efficacy of xialine in patients with xerostomia resulting from radiotherapy for head and neck cancer: A pilot-study Radiother Oncol. 2001;59:157–60
20. Andersen SW, Machin D. Acupuncture treatment of patients with radiation-induced xerostomia Oral Oncol. 1997;33:146–7
21. Blom M, Dawidson I, Fernberg JO, Johnson G, Angmar-Månsson B. Acupuncture treatment of patients with radiation-induced xerostomia Eur J Cancer B Oral Oncol. 1996;32B:182–90
22. Wong RK, Jones GW, Sagar SM, Babjak AF, Whelan T. A phase I-II study in the use of acupuncture-like transcutaneous nerve stimulation in the treatment of radiation-induced xerostomia in head-and-neck cancer patients treated with radical radiotherapy Int J Radiat Oncol Biol Phys. 2003;57:472–80
23. Simcock R, Fallowfield L, Monson K, Solis-Trapala I, Parlour L, Langridge C, et al ARIX: A randomised trial of acupuncture v oral care sessions in patients with chronic xerostomia following treatment of head and neck cancer Ann Oncol. 2013;24:776–83
24. Wong RK, Deshmukh S, Wyatt G, Sagar S, Singh AK, Sultanem K, et al Acupuncture-like transcutaneous electrical nerve stimulation versus pilocarpine in treating radiation-induced xerostomia: Results of RTOG 0537 phase 3 study Int J Radiat Oncol Biol Phys. 2015;92:220–7
25. Saleh J, Figueiredo MA, Cherubini K, Braga-Filho A, Salum FG. Effect of low-level laser therapy on radiotherapy-induced hyposalivation and xerostomia: A pilot study Photomed Laser Surg. 2014;32:546–52
26. Criswell MA, Sinha CK. Hyperthermic, supersaturated humidification in the treatment of xerostomia Laryngoscope. 2001;111:992–6
27. Ameri A, Heydarirad G, Rezaeizadeh H, Choopani R, Ghobadi A, Gachkar L, et al Evaluation of efficacy of an herbal compound on dry mouth in patients with head and neck cancers: A Randomized clinical trial J Evid Based Complementary Altern Med. 2016;21:30–3
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    Keywords:

    Head; management; neck; xerostomia

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