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Xerostomia (dry mouth) and Salivary Swelling after Irradiation Prevention and Treatment

last modified on: Wed, 03/03/2021 - 16:52

see on-line book chapter addressing Radioiodine Sialadenitis: https://link.springer.com/article/10.1007/s40136-014-0041-1

return to: Management of XerostomiaI131 sialadenitis (Radioiodine Sialadenitis)Parotid Sialogram Post Irradiation Stricture

Table 1 Selected Methods to Prevent Sialadenitis from Irradiation

Prevention Strategy

Studies

Study Characteristics

Conclusions

 

 

Radioiodine Irradiation

 

Dose Reduction of I131 administered

Multiple studies including[i],[ii],[iii] 

Human (clinical) study – analyzing effectiveness of thyroid ablation with low dose radioiodine measured by post-treatment rhTSH-stimulated thyroglobulin assessment as well as post-treatment I131 scintigraphy

In appropriately selected cases post-surgical residual thyroid tissue may be successfully ablated with 30 mCi (1.1 GBq) of I131; emphasis is placed on complete surgical excision – to limit the dose required for ablation and in some cases avoid the need for radioidine ablation

Sialogogues (lemon candy) administration at time of I131 tx

Nakada et al 2005 [iv]

Human (clinical) study - sucking lemon candy < 1h (group A) or >24 h (group B) after I131 ingestion

Xerostomia, altered taste and sialadenitis highest in the treated  with candy at the time of treatment (group A)

Parasympathetic stimulation immediately after 131 administration

Silberstein (2008)[v]

Human (clinical) study – randomized controlled study of 60 patients receiving either placebo or pilocarpine 5 mg orally every 8 hours for one week after I131 therapy

No benefit seen in pilocarpine group compared to control – reason for lack of benefit ascribed to success of “Cincinnati regimen’ used for both the study and control groups with equally good results (no acute sialadenitis)

“Cincinnati regimen” intense siarrheic management with hydration during and after I131 treatment

Silberstein 2008 [vi]

oral 8 mg of dexamethasone and 100 mg of dolasetron 2 hours before therapy and every 12 hours for 5 doses after I131 ingestion

2,400 mL of nondairy liquid per day for the week after therapy

Sugar-free gum or candy in the mouth at all times when awake for a week and for the first 3 nights, awaken every three hours to reapply sialogogues and then brush mouth with soft toothbrush and water for one minute 

 

Remarkably low incidence of salivary problems supports further investigation of this approach. Unclear as to contribution provided by dexamathasone (anti-inflammatory) and dolasetron (secretogogue) which were given primarily for their anti-emetic properties

Amifostine (free radical scavenger) administered intravenously prior to I131

Ma et al 2010[vii]

Human (clinical) studies – review of literature focused on two randomized controlled studies

German study Bohuslavizki et al (1998) [viii]

Korean study Kim et al (2008) [ix]

Reviewed of randomized controlled studies concluded there was no radioprotective effect of amifostine on the salivary glands despite inclusion of the early study (Bohuslvizki et al 1998) suggesting there was benefit

 

 

 

 

 

 

External Beam Irradiation

 

Prior to irradiation inject Botulinum toxin to  the glands (chemical denervation) to induce temporary involution

Teymoortash A et al 2009 [x]

Animal (rat) study – botulinum toxin injected to one of the two submandibular glands 14 days before external beam irradiation (20 Gy single dose)

Protective effect of botulinum toxin documented by salivary lymphoscintigraphy and histologic analysis (95 days after treatment)

Prior to irradiation infuse glands with a protein (TLK1B) that facilitates DNA repair and cell survival

Sunavala-Dossabhoy et al 2012 [xi]

Animal (rat) study –deleterious effects of external beam irradiation (16 Gy) attenuated by infusion of submandibular salivary ducts with modified TLK1B protein before XRT

Potential for infusion of protective/reparative protein ‘safer alternative to gene therapy’

During irradiation administer acupuncture three times per week

Meng et al 2011

Human (clinical) study randomizing patients under treatment for nasopharyngeal carcinoma with external beam irradiation

Significantly greater salivary flow and diminished symptoms of xerostomia in treated group possibly related to the acupuncture stimulating the brain or producing neuropeptides

Gene therapy (cDNA for hKGF in adenovirus vector) instilled into submandibular glands before irradiation exploiting function of KGF (keratinocyte growth factor) to regenerate damaged epithelium

Zheng et al 2011[xii]

Animal (mouse) study - infuse glands of 8 week old mice through cannulation and retrograde delivery cDNA viral vector followed versus control  then irradiated (single dose 15 Gy as well as second group with  6 Gy daily fractions for 5 days) with endpoints including stimulated (pilocarpine) salivary flow analysis

Transfer of the hKGF gene to SGs prior to both fractionated and single-dose IR substantially prevents salivary hypofunction. Not yet clear whether salivary parenchymal, endothelial, and/or progenitor cells/stem cells are all targets of the transgenic hKGF.

 

Table 2 Selected Methods to Treat Sialadenitis from Irradiation

 

Treatment Strategy

Study

Study Characteristics

Conclusions

 

 

Radioiodine Irradiation

 

Enhance flow of saliva by gland massage and by  avoiding dehydration; use of sialogogues to stimulate salivary secretion; antibacterial / anti-inflammatory medication as needed

Multiple reports include this regimen as standard [xiii], [xiv]

No critical randomized controlled studies identified for analysis

These recommendations are frequently presented  as adequate treatment for most cases of radioiodine sialadenitis with other interventions considered supplemental to this standard therapy as per trials listed below

 

 

 

 

Pilocarpine administered orally as  parasympathetic agent (non-selective muscarinic agent with mild B-adrenergic activity)

 

Aframian et al (2006) [xv]

Human (clinical) study - 4 of the 5 evaluated patients after xerostomia had developed following I131 (150-550 mCi) were shown to have improved stimulated and unstimulated salivary flow following ingestion of 5 mg pilocarpine

Short-term pilocarpine increased salivary output to ‘open a new avenue’ for treatment of radioiodine-induced xerostomia with large scale long-term study needed

Sialendoscopy Treatments

 

 

 

Sialendoscopy permitting dilation of I131 induced ductal stenosis and clearance of mucus plugs and ‘ductal wash’ with 100 mg hydrocortisone

Nahlieli O et al (2006) [xvi]

Human (clinical) study - 1st description of use of sialendoscopy to treat 15 patients with hydrostatic pressure through ‘continuous lavage’ punctuated by ‘saline torrent’ dilation in each patient with one additional patient treated with a sialoballoon

Successful mechanical dilation of the strictures not always achieved but with ‘excellent toileting’… ‘symptomatic improvement is always achieved”

Sialendoscopy as method to direct balloon or endoscopic sheath dilation of narrowing identified on sialography (no steroid insufflation)

Kim et al (2007) [xvii]

Human (clinical) study – 6 patients with post-I131 strictures addressed with balloon dilation and endoscopic sheath dilation

Three failures out of 6 patients due to total duct obstruction in two patients and one patient with severe stenosis preventing passage of balloon leading to recommendation that interventional sialendoscopy be performed before development of severe symptoms occur.

Sialendoscopy to irrigate debris and instill medication (40 mg of triamcinolone diluted in saline)

Bomeli et al (2009) [xviii]

Human (clinical) study – 12 patient addressed with success in cannulating 27 of 32 targeted glands

Symptom improvement in 9 of 12 patients treated – two of the failures ascribed to inability to cannulate past stenosis or masseteric bend in duct of parotid

Sialendoscopy with dilation of the puncta to introduce the sialendoscope with flushing of the ductal system (no steroid insufflation)

Prendes et al (2012) [xix]

Human (clinical) study – 11 patients with 23 of 24 parotid ducts successfully cannulated; all 5 submandibular ducts cannulated

Complete resolution of symptoms in 6 (54%), partial improvement in 4 (36%) and no improvement in one patient who was subsequently treated with parotidectomy

 

 

External Beam Irradiation

 

Hypnosis as  a method for “optimizing the physiologic environment for salivation by cortical stimulation” and “counteracting negative expectancy”

Schiff E et al 2009 [xx]

Human (clinical) study – prospective study of 12 patients (without a control group) with refractory xerostomia following external beam irradiation evaluated with questionnaire and sialometry

Improvement in symptoms correlated with degree of exposure to hypnosis but did not correlate with stimulated and unstimulated salivary flow which did not improve with hypnosis

Gene Therapy to induce functional water channels in ductal cells to establish and osmotic gradient directing fluid intraluminally

Baum BJ et al 2012[xxi]

Human (clinical) study – phase I/II retrograde instillation of adenovirus vector delivering cDNA for the water channel aquaporin-1 (AGP1) for patients with xerostomia following external beam irradiation

Enhanced parotid flow rate in 6 of 11 treated subjects

 

[i] Mallick U, Harmer C, Yap B, Wadsley J, Clarke S, Moss L, Nicol A, Clark PM, Farnell K, McCready R, Smellie J, Franklyn JA, John R, Nutting CM, Newbold K, Lemon C, Gerrard G, Abdel-Hamid A, Hardman J, Macias E, Roques T, Whitaker S, Vijayan R, Alvarez P, Beare S, Forsyth S, Kadalayil L, Hackshaw A. Ablation with  low-dose radioiodine and thyrotropin alfa in thyroid cancer. N Engl J Med. 2012 May 3;366(18):1674-85. doi: 10.1056/NEJMoa1109589. PubMed PMID: 22551128

[ii] Schlumberger M, Catargi B, Borget I, Deandreis D, Zerdoud S, Bridji B, Bardet  S, Leenhardt L, Bastie D, Schvartz C, Vera P, Morel O, Benisvy D, Bournaud C, Bonichon F, Dejax C, Toubert ME, Leboulleux S, Ricard M, Benhamou E; Tumeurs de la Thyroïde Refractaires Network for the Essai Stimulation Ablation Equivalence Trial. Strategies of radioiodine ablation in patients with low-risk thyroid cancer. N Engl J Med. 2012 May 3;366(18):1663-73. doi: 10.1056/NEJMoa1108586. PubMed PMID: 22551127.)

[iii] Orlov S, Freman JL, Walfish PG: Radioiodine ablation in low-risk thyroid caner. NEJM 2012 Aug 16;367(7): 672

[iv] Nakada K, Ishibashi T, Takei T, Hirata K, Shinohara K, Karoh S, Zhao S, Tamaki N, Noguchi Y, and Noguchi S: Does Lemon Candy Decrease Salivary Gland Damage After Radioiodine Therapy for Thyroid Cancer  J Nucl Med 2005;46:261-266  [Xerostomia, altered taste and sialadenitis highest in the treated  with candy at the time of treatment]

[v] Silberstein EG: Reducing the Incidence of I131 –Induced Sialadenitis: the role of Pilocarpine TheJournal of Nuclear Medicine vol 49 No 4 April 2008 pp 546-549  [No benefit seen in pilocarpine group compared to control – reason for lack of benefit ascribed to success of “Cincinnati regimen’ used for both the study and control groups with equally good results (no acute sialadenitis) ]

[vi] Silberstein EG: Reducing the Incidence of I131 –Induced Sialadenitis: the role of Pilocarpine TheJournal of Nuclear Medicine vol 49 No 4 April 2008 pp 546-549

[vii] Ma C, Xie J, Jiang Z, Wang G, and Zuo S: Does amifostine have radiopreotective effects on salivary glands in high-dose radioactive iodine-treated differentiated thyroid cancer  Eur J Nucl Med Lol Imaging(2010) 37:1778-1785  [Reviewed of randomized controlled studies concluded there was no radioprotective effect of amifostine on the salivary glands]

[viii]  Bohuslavizki KH, Klutmann S, Brenner W, Mester J, Henze E, Clausen M. Salivary gland protection in high-dose radioiodine treatment: resulst of a double blind pacebo-controlled study. J Clin Oncol 1998;16:3542-9

[ix] Kim SJ, Choi HY, Kim IJ, Kim YK, Jun S, Nam HY, et al. Limited cytoprotective effects of amifostine in high-dosee radioactive iodine 131-treated well-differentiated thyroid cancer patients: analysis of quantitative salivary scan. Thyroid 2008;18:325-31

[x] Teymoortash A, Muller F, Juricko J, Bieker M, Mandic R, Librizzi D, Hoffken H, Pfestroff A, and Werner JA: Botulinum toxin prevents radiotherapy-induced salivary gland damage.Oral Oncology 45 (2009) 737-739

[xi] Sunavala-Dossabhoy G, Palaniyandi S, Richardson C, De Benedetti A, Schrott L, and Caldito G: TAT-Mediated Delivery of Tousled Protein to Salivary Glands Protects Against Radiation-Induced Hypofunction. In J Radiation Oncol Biol Phys, Vol. 84, No.1, pp 257-265, 2012

[xii] Zheng C, Cotrim AP, Rowzee A, Swaim W, Sowers A, Mitchell JB, and Baum BJ: Prevention of radiation-induced salivaryhypofunction following hKGF gene delivery to murine submandibular glands. Clin Cancer Res. 2011 May 1;17(9):2842-51

[xiii] Kim JW, Han GS, Lee Sh, Lee DY, Kim YM. Sialeoendoscopic treatment for radioioiodine induced sialadaenitis. Laryngoscope 2007;117(1):133-136

[xiv] Prendes BL, Orloff LA, and Eisele DW: therapeutic Siaolendoscopy for the management of Radioiodine sialadenitis. Arch Otolaryngol Head Nekc surg. 2012;138(1):15-19

[xv] Aframian DJ, Helcer M, Livni D, Markitziu A: Pilocarpine for the treatment of salkviary glands’ impairment caused by radioiodine therapy for thyroid cancer. Oral Diseases 2006 12, 297-300 [Short-term pilocarpine increased salivary output to ‘open a new avenue’ for treatment of radioiodine-induced xerostomia with large scale long-term study needed]

[xvi] Nahlieli O and Nazarian Y: Sialadenitis following radioiodine therapy – a new diagnostic and treatment modality. Oral Disease (2006) 12, 476-479 [1st description of use of sialendoscopy to treat 15 patients with hydrostatic pressure through ‘continuous lavage’ punctuated by ‘saline torrent’ dilation in each patient with one additional patient treated with a sialoballoon]

[xvii] Kim JW, Han GS, Lee Sh, Lee DY, Kim YM. Sialeoendoscopic treatment for radioioiodine induced sialadaenitis. Laryngoscope 2007;117(1):133-136  [Three failures out of 6 patients due to total duct obstruction in two patients and one patient with severe stenosis preventing passage of balloon leading to recommendation that interventional sialendoscopy be performed before development of severe symptoms occur.]

[xviii] Bomeli SR, Schatkin B, Carrau RL, Walvekar RR. Interventional sialendoscopy for treatment of radioiodine-induced sialadenitis. Laryngoscope 2009;1172009;119(5)862-867

[xix] Prendes BL, Orloff LA, and Eisele DW: therapeutic Siaolendoscopy for the management of Radioiodine sialadenitis. Arch Otolaryngol Head Nekc surg. 2012;138(1):15-19

[xx] Schiff E, Mogilner JG, Sella Eyal Sella, Doweck I, Hershko O, Ebn-Ayre E, and Yarom N: Hypnosis for Postraidation Xerostomia in Head and Neck Cancer Patients: A Pilot Study  Journal of Pain and Symptom Management. Vol 37 No.6 June 2009

[xxi] Baum BJ, Alevizos I, Zheng, Cotrim AP et al: Early responses to adenoviral-mediated transfer of the aquaporin-1 DNA for radiation-induced salivary hypofunction. PNAS Nov 20, 2012 vol. 109 no. 47 19403-7