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Taste Loss and Recovery Following Radiation TherapyDepartment of Oral & Maxillofacial Surgery and Diagnostic Sciences, University of Florida Health Science Center, 1600 SW Archer Road, Room D8-6, PO Box 100414, Gainesville, FL 32610-0414, USA Correspondence: * corresponding author, psandow{at}dental.ufl.edu
Previous investigators have reported deficits in taste acuity in patients following radiation therapy for oropharyngeal cancer. In the present longitudinal study, 13 patients (mean age = 51.6 yrs) received conventional or hyperfractionated radiotherapy (63–76.8 Gy) for primary tumors of the oropharynx. One or both parotid glands and at least two-thirds of the tongue were included in the radiation field. Smell recognition and taste detection thresholds were determined at baseline, 1 month, 6 months, and 1 year post-radiation. Differences for smell recognition and the 4 taste qualities were assessed (independently) at the 4 time intervals, with a one-way ANOVA. Smell recognition was unaffected by radiation. There were significant elevations in thresholds for sweet (p < 0.005), salty (p < 0.005), bitter (p < 0.005), and sour (p< 0.001) during radiation therapy that were restored to baseline levels at 6 months and 1 year after radiation. This study demonstrated that radiation-induced taste deficits can be recovered by 6 months.
Key Words: radiation • dysgeusia • recovery • taste
Taste deficits as a consequence of head and neck radiation were first described as "taste hallucinations" or "blindness of the mouth" (MacCarthy-Leventhal, 1959). Today, this is more correctly referred to as post-irradiation gustatory dysfunction. It is a common problem among head and neck radiation therapy patients (Vissink et al., 2003a,b) that is often transitory; however, there has been very little systematic research in this area to assess the temporal course of taste loss and recovery following radiation. Post-irradiation gustatory dysfunction has been reported to occur 2 to 3 days after the onset of radiation therapy, with doses as small as 200–400 cGy. Taste bud degeneration typically occurs 6 to 7 days after irradiation. Radiation-induced taste dysfunction can be associated with damage to either the intragemmal nerve cells or taste cells, or both (Nelson, 1998). Because nerve fibers are non-dividing and do not proliferate, damage to these cells is unlikely to recover, and the related radiation-induced taste loss would not recover. However, damage to taste cells, which replenish approximately every 10 days, would likely recover at least partially, unless the proliferative capacity of the receptor cells is disrupted. Taste buds are the anatomic structures which house the receptor cells that subserve the sense of taste. The taste buds are located principally on the tongue, but are also found on the palate, pharynx, epiglottis, and larynx. These structures are typically within the irradiated field for the treatment of oral cancers. The tongue is covered with specialized structures named papillae, which contain the taste buds. Each taste bud contains 50 to 100 taste receptor cells, which are in a constant rate of turnover, having a life span of approximately 10–11 days. However, if the nerve fiber that innervates a taste bud is cut or injured, the taste bud will degenerate (Nelson, 1998). Radiation-induced smell changes are less commonly noted, because olfactory receptors usually lie outside the irradiated field. Acute changes in smell acuity have been reported when the olfactory receptors are in the direct field of radiation exposure (Ophir et al., 1988). Studies of the temporal course of radiation-induced taste deficits or loss and subsequent recovery are limited (Mossman et al., 1982; Fernando et al., 1995; Maes et al., 2002; Zheng et al., 2002). Several reports assessed these changes in different groups of patients at different time periods following radiation. However, these cross-sectional studies did not control for the treatment regimens as well as for individual differences in taste experience. This prospective longitudinal study assessed the temporal course for radiation-induced deficits and recovery of the chemical senses following treatment within individuals. More specifically, we assessed the sense of smell and all 4 taste qualities (sweet, salt, bitter, and sour) prior to (baseline), during, 6 mos, and 1 yr after head and neck radiation therapy in the same patient, to control for inter-participant variability. We included the smell or olfactory testing at each of the 4 sessions, to rule out olfactory damage as a variable in determining whether the radiation-induced changes in subjective taste perception might be related to flavor (a combination of both taste and smell). The temporal course of potential chemosensory loss and recovery was assessed.
Participants in the study were at least 21 yrs of age, both dentate and edentulous, with tumors of the head and neck region. Patients receiving radiation to the nasal cavity or ethmoid areas were excluded from the study. We included five healthy control individuals of similar age, to assess whether the cancer patients had coincident taste and smell deficits at baseline. The participants’ rights were protected by an appropriate institutional review board, and informed consent was granted. Thirteen patients were followed for 1 yr. Eleven patients completed all 4 testing sessions, including the last session at 1 yr after radiation therapy. One patient did not tolerate the sweet and bitter, and another did not tolerate sweet and salty at 1 mo, both because of nausea. There were ten male (mean age = 55.5 ± 13.4 yrs) and three female participants (mean age = 45.0 ± 5.6 yrs), aged 40 to 75 yrs. Two patients reported smoking less than 1 pack of cigarettes daily, and four patients reported weekly alcohol consumption while enrolled in the study. Ten patients had squamous cell carcinoma, one had adenoid cystic carcinoma, one had sarcoma, and one had lymphoepithelioma. All radiation therapy treatment fields included one or both parotid glands and at least the posterior two-thirds of the tongue. The total tumor dose ranged from 63 Gy to 76.8 Gy, delivered over 5 to 7 wks, with a mean dose of 69.3 Gy. Six patients received 120 cGy, twice daily, and seven patients received 180–200 cGy, daily. None of the participants received Intensity Modulated Radiation Therapy (IMRT) nor experienced an interruption in radiation therapy treatment. Three of the 13 patients (23%) also received concomitant cisplatinum. Two healthy females (mean age = 47.0 ± 5.7 yrs) and three healthy males (mean age = 48.7 ± 21.1 yrs) served as controls. For each patient, taste and smell function was assessed at baseline prior to the initiation of radiation therapy (baseline, BL), 4 wks after the initiation of (during) radiation therapy (1 mo), 6 mos after the completion of radiation therapy (6 mos), and at least 1 yr after the completion of radiation therapy (12 mos). Threshold for each taste quality (sweet, salty, bitter, sour) was determined, separately, by the Method of Limits (Gescheider, 1976). In this procedure, taste samples are systematically provided to the participant to "swish" and expectorate before the participant indicates whether or not he/she tastes anything. In the ascending Method of Limits, stimulus concentrations are increased until the participant perceives a taste. In the descending Method of Limits, the initial concentrations are well within the perceived range and are decreased in successive trial steps until the taste sample is no longer perceived. For each series, successive concentrations of solutions were increased (or decreased in the descending Method of Limits) by 0.25 log units of molar concentration. Reagent-grade chemicals and double-distilled de-ionized water were used to prepare the solutions. Stimulus concentrations ranged from 0.000032 to 1.0 molar for sucrose (sweet), from 0.00001 to 0.56 molar for sodium chloride (salty), from 0.000000018 to 0.001 molar for quinine sulfate (bitter), and from 0.000001 to 0.01 molar for citric acid (sour). Distilled water from the same source, without solute, served as a blank stimulus for the threshold determination procedure. Prepared solutions were stored in 500-mL glass-stoppered reagent bottles at 4°C between sessions, and were brought to room temperature for the experimental session. Stimuli were dispensed to each participant in 10-mL samples from disposable pipette tips. Participants used a bottle of distilled water for rinsing between trials. Thresholds for all taste qualities were determined in the same testing session. A two-alternative, forced-choice procedure was used for each trial. The participant was presented with 1 pipette of the taste solution and then was asked to rinse with distilled water and expectorate. The participant was then presented with a pipette of distilled water and asked to choose the pipette with the taste solution. Before the next taste solution was tested, the participant was required to rinse with water and expectorate. The presentation of the 2 solutions, both tastant and water, was in random order to control for order effects. The taste solution and distilled water were delivered directly to the taste buds of the tongue. A crossover was recorded with changes from the last concentration not perceived and the concentration of the first that was perceived. The procedure was continued until 4 crossovers were determined for each quality. The geometric mean (average log value) of the 4 crossover points for each quality was defined as the threshold. The sense of smell was assessed based on the 40-item version of the University of Pennsylvania Smell Identification Test (UPSIT), a standardized "scratch and sniff" test of olfactory function (Deems et al., 1991). Rather than assessing perceptual thresholds, this test assessed detection and recognition of suprathreshold concentrations of a variety of odorants. UPSIT significantly correlates with traditional methods of odor detection thresholds. An individual participant’s test results were scored as the number of selections that were correct, with a maximum score of 40. Differences for smell recognition and the 4 taste qualities were assessed independently at the 4 time intervals (BL, 1 mo, 6 mos, and 12 mos) with a one-way ANOVA.
There were no differences between the patient group (P) and control group (C) in the measures of smell and taste sensitivity at baseline (SMELL—P = 33.0, C = 35.8; TASTE—sweet, P = 0.0123, C = 0.0237; salty, P = 0.006, C = 0.012; bitter, P = 0.000013, C = 0.000035; sour, P = 0.00031, C = 0.00017). This finding supports the understanding that the oral cancer does not alter chemosensory sensitivity. Further, there were no significant differences between conventional vs. hyperfractionated courses of radiotherapy, smokers vs. non-smokers, and alcohol users vs. non-users.
The mean taste thresholds (concentrations) for sweet, salty, bitter, and sour at baseline (BL), 4 wks (1 mo), 6 mos (6 mos), and 1 yr (12 mos) are shown (Figs. 1
The findings from this longitudinal investigation demonstrated that radiation-induced deficits in taste sensitivity are evident at 1 mo after the initiation of therapy, but that recovery is apparent at 6 mos and 1 yr post-treatment. Further, olfactory function was unaffected, due to the fact that the olfactory receptors were outside the irradiated field. Individual variability in treatment protocols and taste experience was controlled for by the use of a within-participant repeated-measures design, and the use of change scores (thresholds and smell recognition) from baseline in assessing radiation effect and recovery. By repeating the testing session at 6 mos and 1 yr, we could assess the time frame for functional regeneration of primary afferent nerves and taste receptor cells. Taste decrements have been reported as a significant finding in cancer patients. For example, an elevated taste threshold for sweet has been reported in 25 patients and a lowered taste threshold for bitter in 16 cancer patients, with a perceived taste abnormality being greater with more advanced disease (DeWys and Walters, 1975). In contrast, we found no significant elevation in taste threshold or smell acuity in cancer patients prior to receiving radiation therapy, when compared with control participants. The taste decrements that we observed at 1 mo (during radiation therapy) are consistent with previous reports. However, we observed uniform deficits for the 4 modalities that recovered at 6 mos. In contrast, there are several reports of a gradual but incomplete recovery of taste after therapy, especially for bitter and salty, when measured at 1–2 yrs (Maes et al., 2002) and 1–7 yrs (Mossman et al., 1982) after the completion of radiotherapy. Those reports did not include studies of individual patients for those time periods, but, rather, assessed different groups of patients at various times following treatment. Thus, these studies did not account for individual differences in treatment protocols and taste experience. In the Maes et al. report (2002), four separate groups of head and neck cancer patients were assessed at baseline (n = 17), 2 mos (n = 17), 6 mos (n = 17), and 12–24 mos (n = 22) post-treatment. There were only 3 concentrations for each of the 4 taste qualities: sweet (sucrose), salt (NaCl), sour (HCl), and bitter (urea). For each trial, participants were requested to identify the trial as "neutral" or one of the 4 taste qualities. Taste loss was reported for all time periods, and the minimum residual taste loss noted at 1–2 yrs was 27%. In contrast, in our longitudinal study, which followed all patients until 1 yr post-treatment, we noted deficits at 1 mo and full recovery at 6 mos post-treatment. In a more recent prospective study of 40 head and neck radiotherapy patients, in whom the time-course and degree of taste deficits were evaluated, the ascending but not descending method of limits-threshold testing was used (Zheng et al., 2002). These investigators also reported that all 4 taste qualities, especially bitter, were affected during radiotherapy, and that recovery occurred by 6 mos after the completion of radiotherapy. Further, it has been suggested that post-radiation deficits in taste functioning may be related to radiation damage to the salivary glands and associated xerostomia, because saliva is the solvent for gustatory stimuli (Bolze et al., 1982; Christensen et al., 1984; Spielman, 1998; Tomita and Osaki, 1990; Epstein et al., 1999; Zheng et al., 2002). However, at least two studies, evaluating the effects of radiation therapy on taste and salivary function in man, have concluded that there is no strong relationship existing between salivary and taste dysfunction (Mossman et al., 1982; Zheng et al., 2002). Finally, the time-course for recovery of taste in the present study suggested that the site of radiation damage is at the level of the taste cells, rather than the intragemmal nerve fibers. If there was nerve damage, it is unlikely that taste would be restored at 6 mos. Further, the finding of complete taste recovery in all patients in these well-characterized groups provides encouraging evidence regarding the transient nature of taste decrements for patients undergoing similar treatment protocols.
This work was supported by the University of Florida College of Dentistry. Received for publication November 22, 2004. Revision received March 17, 2006. Accepted for publication April 21, 2006.
Journal of Dental Research, Vol. 85, No. 7,
608-611 (2006) This article has been cited by other articles:
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