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Emerging Technology List
SUBMANDIBULAR GLAND TRANSFER FOR
PRESERVATION OF SALIVARY FUNCTION
CANADIAN COORDINATING
OFFICE FOR HEALTH
TECHNOLOGY ASSESSMENT
NO. 21
Technology:
JULY 2004
An estimated 6,400 Canadians were diagnosed with head and neck cancers in 2003.1
The standard treatment for these cancers is radiation therapy in combination with
surgery to remove the tumour. Unfortunately, radiation therapy can damage the salivary glands. This reduces the flow and changes the chemical composition of saliva,
causing xerostomia (dry mouth) and its associated side effects, such as dental cavities; gum disease; and problems with speaking, tasting, swallowing and digesting.
Xerostomia, which is a common and usually permanent adverse effect of head and
neck radiotherapy, affects an individual’s quality of life.2
Submandibular gland transfer is a surgical procedure during which one of the submandibular salivary glands is repositioned into the submental space of the lower jaw.
As a result, the gland can be shielded from most of the radiation administered during
treatment and its salivary function maintained. The operation is also known as the
Seikaly and Jha procedure, after the two Edmonton physicians, Dr. Hadi Seikaly and
Dr. Naresh Jha, who developed it.3
Purpose:
Saliva is produced by several glands. The major salivary glands (parotid, submandibular and sublingual glands) occur in pairs, with one of each gland on either
side of the head (Figure 1). These glands produce about 90% of the saliva, while
minor salivary glands, in the lining of the mouth and throat, produce the remainder.4,5
The submandibular and parotid glands produce about 65% and 20% to 25% respectively of unstimulated saliva, while the parotid glands produce about 50% of the
stimulated saliva that flows during eating.6,7
Figure 1: Salivary glands
Reproduced with permission from Dr. Naresh Jha.
The Canadian Coordinating Office for Health Technology Assessment (CCOHTA)
is a non-profit organization funded by the federal, provincial and territorial governments. (www.ccohta.ca)
Emerging Technology List
SUBMANDIBULAR GLAND TRANSFER FOR
PRESERVATION OF SALIVARY FUNCTION
Current Regulatory
Status:
CANADIAN COORDINATING
OFFICE FOR HEALTH
TECHNOLOGY ASSESSMENT
As submandibular gland transfer is a surgical procedure, it does not require Health
Canada licensing.
Description:
Submandibular gland transfer is usually performed during the surgery to remove
primary tumours, before the start of radiation therapy.8 The transfer surgery can also
be undertaken in patients who require radiation therapy but not surgical removal of
their tumours. Submandibular gland transfer is performed using the salivary gland on
the contralateral (opposite) side to that of the primary tumour. Submandibular gland
transfer is not an option for patients with cancer of the the oral cavity (the mouth)
or for those who have bilateral neck lymph node involvement.8 A selective neck
dissection is done first. Suspicious nodes and all level 1 lymph nodes (submental and
submandibular) are sent for frozen section evaluation. If cancer is found, the transfer
is abandoned and a formal neck dissection is performed. The borders of the transferred gland are marked with 25 mm gauge wire to help identify it during radiotherapy.
Submandibular gland transfer is a simple procedure that adds about 45 minutes to the
operating time.2 Dr. Jha estimates that up to three-quarters of patients with head and
neck cancers could benefit from the use of this surgical procedure.8
Cost:
A submandibular gland transfer is not listed in provincial physician fee schedules,
information on the cost of the procedure is unavailable. If the surgery becomes widely
adopted, fee schedules should be revised to reflect the additional surgical time
involved. Overall health care costs might be reduced through reduced hospitalization
for post-treatment complications (such as dehydration or the inability to eat or drink
due to mouth sores and pain) and decreased expenditures on drug and other therapies
to treat xerostomia. For example, the manufacturer’s price (excluding dispensing fees
and retail markup) for each 5 mg pilocarpine hydrochloride (Salagen®) tablet, a drug
commonly used to treat xerostomia, is about C$1.9 The typical dosage is three or
four tablets daily and if the treatment is tolerated by and effective for the patient, it
is continued for the rest of his or her life.
Dental costs for the treatment of the tooth decay and gum disease associated with
xerostomia could be reduced if submandibular gland transfer can maintain salivary
function. This is being investigated as part of the phase III randomized, multicentre
study comparing pilocarpine and submandibular salivary gland transfer. A recent US
study of drug treatments for radiation-induced xerostomia concluded that “the cost of
maintaining and restoring dentition following radiation-induced xerostomia can be
tremendous….Given the number of teeth that may be involved and the ongoing
nature of the requirement for dental treatment in patients with radiation-induced
xerostomia, it is easy to see how the costs of maintaining oral and dental health can
escalate rapidly. Periodontal treatment and time lost from work only add to these
expenses.”10
The Canadian Coordinating Office for Health Technology Assessment (CCOHTA)
is a non-profit organization funded by the federal, provincial and territorial governments. (www.ccohta.ca)
Emerging Technology List
SUBMANDIBULAR GLAND TRANSFER FOR
PRESERVATION OF SALIVARY FUNCTION
Evidence:
CANADIAN COORDINATING
OFFICE FOR HEALTH
TECHNOLOGY ASSESSMENT
Several case series reports describe early experiences with submandibular gland
transfer.11,12 A 2003 paper by Jha et al. reports on 84 patients in a phase II clinical
trial.12 Of these patients, 60 underwent submandibular gland transfer. Nine patients
did not subsequently receive radiation therapy and in another eight patients, the
transferred gland was not shielded from radiation because of the proximity of the
cancer. As a result, 43 patients underwent submandibular gland transfer followed by
radiation therapy. The University of Washington quality of life (QOL) questionnaire
was used to measure xerostomia before treatment began and at several points posttreatment. Six months after the end of radiation treatment, 71% of patients reported
no or minimal xerostomia. Among the patients who had submandibular gland transfer but no shielding from radiation due to the proximity of the cancer and those who
did not have submandibular gland transfer, 71% had moderate to severe xerostomia.12
Similarly, a Dutch study of 39 long-term survivors of head and neck cancers who
had undergone standard radiation treatment found that 64% continued to suffer from
moderate to severe xerostomia.13
An earlier paper reporting on 25 patients in the submandibular gland transfer study
found that the amount of saliva after surgery and radiation treatment remained normal. Most patients found that their chewing and swallowing were unchanged, though
many reported an alteration in taste.2 Head and neck cancer patients often suffer
from oral mucositis (mouth ulcers) that make eating painful. The patients who
underwent salivary gland transfer had less oral mucositis and candidiasis (a fungal
infection of the mouth) than head and neck cancer patients undergoing the typical
post-treatment experience. Most did not require a liquid diet and their weight
remained stable.
A phase II multicentre study of submandibular salivary gland transfer to prevent
radiation-induced xerostomia is underway in North America under the auspices of
the Radiation Therapy Oncology Group (RTOG).14 The trial will involve 48 patients
and will assess the reproducibility of the submandibular salivary gland transfer procedure, the rate and severity of xerostomia after this procedure, the quality of life of
patients and their health outcomes (cancer recurrence and overall survival rates).
A phase III multicentre trial comparing drug therapy (pilocarpine hydrochloride) to
salivary gland transfer is ongoing at centres in Alberta, Manitoba, Quebec and
Newfoundland. The Cross Cancer Institute, in Edmonton AB has data on over 170
patients treated through various protocols (Naresh Jha, Alberta Cancer Board,
Edmonton: personal communication, 2004 Mar 22).
The Canadian Coordinating Office for Health Technology Assessment (CCOHTA)
is a non-profit organization funded by the federal, provincial and territorial governments. (www.ccohta.ca)
Emerging Technology List
SUBMANDIBULAR GLAND TRANSFER FOR
PRESERVATION OF SALIVARY FUNCTION
Available Alternative
Technologies:
CANADIAN COORDINATING
OFFICE FOR HEALTH
TECHNOLOGY ASSESSMENT
Treatments for xerostomia include saliva substitutes (such as the use of artificial saliva)
and saliva stimulants (such as the use of sugar-free mints or chewing gum; or drug
therapies). Saliva substitutes may temporarily reduce dry mouth, but they have little
effect on the maintenance of dental health. Patients reportedly find little difference in
comfort between using artificial saliva or water.15
Saliva stimulants may reduce xerostomia and other conditions related to salivary
gland dysfunction.16 Pilocarpine hydrochloride (Salagen®) is often used to treat xerostomia, but the drug is contraindicated for some patients (for example, asthmatics or
those with significant cardiovascular disease).17 Moreover, only one- to two-thirds of
patients will benefit from pilocarpine hydrochloride and it may take weeks for the
treatment to take effect.15 The adverse effects, which are considered minor, include
sweating, flushing, increased urinary frequency, blurred vision and tachycardia (rapid
heart beat).2,17
Amifostine (Ethyol®) is a chemoprotectant that may be given intravenously before
each session of radiation therapy to lessen some side effects, including xerostomia.
Its adverse effects include nausea and a decrease in blood pressure. Patients receiving
amifostine must be monitored for signs of toxicity. Its subcutaneous administration,
which appears to be as effective yet less toxic, is being investigated in clinical studies.15 A Cochrane Collaboration systematic review of the effectiveness of drug therapies used in the prevention and treatment of salivary gland dysfunction due to radiation therapy is underway.16
Intensity modulated radiation therapy (IMRT) may be used to decrease the exposure
of parotid salivary glands to radiation. A study by Lin et al. found that this reduces
xerostomia and improves the quality of life for patients after treatment.18 An international, randomized controlled trial of parotid-sparing IMRT in patients with head and
neck cancer is underway.19
Alternative therapies for the treatment of xerostomia, such as acupuncture and electrostimulation, have been used, but there is little evidence of their effectiveness.20
Salivary gland gene therapy is also being investigated. Only data from animal studies
are available and the clinical use of this procedure is years away.6,21,22
Commentary:
The preliminary study results of submandibular gland transfer look promising. This
surgical procedure may improve the quality of life and health of many head and neck
cancer patients after radiation therapy. Clinical trials to determine the advantages
of the procedure and its effect on other health outcomes, particularly long-term
survival, are ongoing.
The Canadian Coordinating Office for Health Technology Assessment (CCOHTA)
is a non-profit organization funded by the federal, provincial and territorial governments. (www.ccohta.ca)
Emerging Technology List
SUBMANDIBULAR GLAND TRANSFER FOR
PRESERVATION OF SALIVARY FUNCTION
References:
CANADIAN COORDINATING
OFFICE FOR HEALTH
TECHNOLOGY ASSESSMENT
1. National Cancer Institute of Canada, Canadian Cancer Society. Canadian Cancer Statistics 2003.
Toronto: The Society; 2003. Available:
http://www.cancer.ca/vgn/images/portal/cit_776/61/38/56158640niw_stats_en.pdf (accessed 2004
Mar 31).
2. Heck K. Prevention of radiation induced xerostomia and improved quality of life: submandibular
salivary gland transfer. Can J Med Radiat Technol 2003;34(3):10-6. Available:
http://www.camrt.ca/french/publications/pdf/journalFall.pdf (accessed 2004 Mar 13).
3. Hodges D. Moving salivary glands may prevent dry-mouth. Med Post 2003;39(17):1,60.
4. Salivary glands. Alexandria (VA): American Academy of Otolaryngology--Head and Neck
Surgery; 2002. Available: http://www.entnet.org/healthinfo/throat/salivary.cfm (accessed 2004
Mar 24).
5. Liu R, Seikaly H, Jha N. Anatomic study of submandibular gland transfer in an attempt to prevent
postradiation xerostomia. J Otolaryngol 2002;31(2):76-9.
6. Seikaly H. Xerostomia prevention after head and neck cancer treatment. Arch Otolaryngol Head
Neck Surg 2003;129(2):250-1.
7. Jha N, Seikaly H, Jacobs JR, Ewan AJB, Weymuller EA, chairs. A phase II study of submandibular salivary gland transfer to the submental space prior to start of radiation treatment for prevention of radiation-induced xerostomia in head and neck cancer patients: RTOG 0244.
Philadelphia: Radiation Therapy Oncology Group, American College of Radiology; 2003.
Available: http://www.rtog.org/members/protocols/0244/0244.pdf.
8. Basky G. Saving saliva function during treatment for head and neck cancer. CMAJ
2000;162(7):1035. Available: http://www.cmaj.ca/cgi/reprint/162/7/1035-a.pdf (accessed 2004
Mar 17).
9. Association Québécoise des pharmaciens propriétaires. Liste de l'AQPP. Montreal: l'Association;
2004 Feb.
10. Taylor SE. Efficacy and economic evaluation of pilocarpine in treating radiation-induced xerostomia. Expert Opin Pharmacother 2003;4(9):1489-97.
11. Jha N, Seikaly H, McGaw T, Coulter L. Submandibular salivary gland transfer prevents radiationinduced xerostomia. Int J Radiat Oncol Biol Phys 2000;46(1):7-11.
12. Jha N, Seikaly H, Harris J, Williams D, Liu R, McGaw T, et al. Prevention of radiation induced
xerostomia by surgical transfer of submandibular salivary gland into the submental space.
Radiother Oncol 2003;66(3):283-9.
13. Wijers OB, Levendag PC, Braaksma MM, Boonzaaijer M, Visch LL, Schmitz PI. Patients with
head and neck cancer cured by radiation therapy: a survey of the dry mouth syndrome in longterm survivors. Head Neck 2002;24(8):737-47.
14. Phase II study of salivary gland transfer surgery prior to radiotherapy for the prevention of radiation-induced xerostomia in patients with head and neck cancer [clinical trial]. In: Cancer.gov
[database online]. Bethesda (MD): National Cancer Institute; 2003. Available:
http://cancer.gov/clinicaltrials/RTOG-0244 (accessed 2004 Mar 25).
15. Eisbruch A, Rhodus N, Rosenthal D, Murphy B, Rasch C, Sonis S, et al. The prevention and
treatment of radiotherapy - induced xerostomia. Semin Radiat Oncol 2003;13(3):302-8.
16. Davies AN, Maytum CM, Chambers EJ, Hanks GW. Parasympathomimetic drugs for the prevention and treatment of salivary gland dysfunction due to radiotherapy [Protocol for a Cochrane
review]. In: The Cochrane Library, Issue 1. Chichester (UK): John Wiley & Sons; 2004.
17. Canadian Pharmacists Association. Compendium of pharmaceuticals and specialties. Ottawa: The
Association; 2003.
18. Lin A, Kim HM, Terrell JE, Dawson LA, Ship JA, Eisbruch A. Quality of life after parotid-sparing IMRT for head-and-neck cancer: a prospective longitudinal study. Int J Radiat Oncol Biol
Phys 2003;57(1):61-70.
The Canadian Coordinating Office for Health Technology Assessment (CCOHTA)
is a non-profit organization funded by the federal, provincial and territorial governments. (www.ccohta.ca)
Emerging Technology List
SUBMANDIBULAR GLAND TRANSFER FOR
PRESERVATION OF SALIVARY FUNCTION
CANADIAN COORDINATING
OFFICE FOR HEALTH
TECHNOLOGY ASSESSMENT
19. Nutting C. An international multi-centre randomised study of parotid-gland sparing intensitymodulated radiotherapy in patients with head and neck cancer [ongoing project]. In: National
Research Register, Issue 1 [database online]: Update Software; 2004. Pub ID: N0258113048.
Available: http://www.update-software.com/National/search.htm (accessed 2004 Mar 24).
20. Brennan MT, Shariff G, Lockhart PB, Fox PC. Treatment of xerostomia: a systematic review of
therapeutic trials. Dent Clin North Am 2002;46(4):847-56.
21. Baum BJ, Goldsmith CM, Kok MR, Lodde BM, van Mello NM, Voutetakis A, et al. Advances in
vector-mediated gene transfer. Immunol Lett 2003;90(2-3):145-9.
22. Kuska B. Researchers report progress in salivary gland gene transfer [news release]. Bethesda
(MD): National Institute of Dental and Craniofacial Research; 2004. Available:
http://www.nidcr.nih.gov/news/03102004.asp (accessed 2004 Apr 1).
CCOHTA thanks Dr. Naresh Jha, Cross Cancer Institute and Division of Radiation
Oncology, University of Alberta, for his comments on a draft of this summary.
This summary was prepared by Leigh-Ann Topfer, MLS; CCOHTA.
This series highlights medical technologies that are not yet in widespread use in Canada and that
may have a significant impact on health care. The contents are based on information from early
experience with the technology; however, further evidence may become available in the future.
These summaries are not intended to replace professional medical advice. They are compiled as
an information service for those involved in planning and providing health care in Canada.
These summaries have not been externally peer reviewed.
ISSN 1499-108X (online only)
The Canadian Coordinating Office for Health Technology Assessment (CCOHTA)
is a non-profit organization funded by the federal, provincial and territorial governments. (www.ccohta.ca)