Radiotherapy-induced taste impairment

Changes in taste perception occur in a significant proportion of cancer patients. Among cancer patients treated with radiotherapy (RT) in head and neck area, the vast majority reports an altered taste sense during and after treatments. Taste impairment starts a few weeks after the beginning of irradiation, and almost all such patients experienced loss of taste acuity at a dose of 60 Gy. Some studies investigated the four basic taste intensities (sweet, salty, sour and bitter) and the umami taste, and several of these reports identified diminished threshold sensitivity for at least one taste quality. Six months to one year after RT, taste acuity recovers to its previous level in many patients, but some patients show incomplete or no recovery even several years later. Taste impairment has profound effects on patients' quality of life because is associated with weight loss through reduced appetite and altered patterns of food intake. Damage to the major salivary glands during head and neck RT leads to disturbance in taste acuity. With the implementation of new radiation techniques, such as conformal and intensity-modulated RT in head and neck irradiation, the late-radiation effects can probably be reduced, but the remaining sequelae are still bothersome to the patients.     

Relation between acute and late irradiation impairment of four basic tastes and irradiated tongue volume in patients with head-and-neck cancer

PURPOSE: Taste loss is a major cause of morbidity in patients undergoing head-and-neck irradiation. The relationship between the time course and the degree of taste disorder was studied in both acute and late phases. METHODS AND MATERIALS: Taste ability was measured by the taste threshold for the four basic tastes using a filter paper disc method in patients before, during, and after radiotherapy. The subjects were divided into two groups. In Group A, the radiation fields included most of the tongue (n = 100), and in Group B the radiation fields did not include the tip of the tongue (n = 18). RESULTS: In Group A, there was a significant impairment of the threshold of all four basic tastes at 3 weeks after starting radiotherapy (RT), and this impairment remained at 8 weeks (p < 0.05). This was not seen in Group B. In Group A, there was no significant difference in the patterns of taste sensitivity change between the high-dose (>20 Gy) and low-dose (< or =20 Gy) groups. In the late phase, recovery of taste loss was seen in both groups since 4 months after completing RT. CONCLUSIONS: Unless the anterior part of the tongue was irradiated, taste loss was not observed during RT. When the anterior part of the tongue was irradiated, a difference by radiation dose was not observed in the taste loss pattern. Additionally, radiation-induced taste dysfunction appears to be a temporal effect.     

Long-term effects of radiotherapy on taste and salivary function in man

The long-term effects of radiotherapy on taste and salivary function were studied in 13 patients treated by radiation 1–7 years previously for tumors of the head and neck. Taste function was quantitatively evaluated using a standard forced choice, three-stimulus-drop technique for the determination of detection and recognition thresholds and a forced-scaling technique for the determination of taste intensity responsiveness. Parotid salivary function was quantitatively evaluated by determination of flow rate and protein secretion rate. Nine of the 13 patients studied (69%) had measurable taste loss; every patient who had radiotherapy including the parotid glands had measurable salivary dysfunction. Our results demonstrate that curative courses of radiotherapy for tumours of the head and neck may result in long-term changes in taste and salivary function. From the present study, the maximum tolerance doses resulting in a 50% complication rate 5 years after treatment (TD 50/5) are estimated to be 40–65 Gy for xerostomia and 50–65 Gy for taste loss. Therefore, in a standard treatment regimen for tumors of the head and neck, with curative intent, gustatory and salivary gland tissues frequently sustain maximum tolerance injury.     

Radiation-induced changes in gustatory function: comparison of effects of neutron and photon irradiation.

Changes in gustatory function were measured in 51 patients with various forms of cancer who received radiation to the head and neck region. Forty patients (group I) were treated with conventional photon radiation (e.g. 66 Gy/7 weeks), and 11 patients (group II) were treated with cyclotron produced fast neutrons (e.g. 22 Gy/7 weeks). Taste acuity was measured for four taste qualities (salt, sweet, sour and bitter) by a forced choice-three stimulus drop technique which measured detection and recognition thresholds and by a forced scaling technique which measured taste intensity responsiveness. Subjective complaints of anorexia, dysgeusia, taste loss and xerostomia were also recorded. Patients were studied before, during and up to two months after therapy.Prior to therapy, detection and recognition thresholds, intensity responsiveness and the frequency of subjective complaints in patients from groups I and II were statistically equivalent. During and up to 2 months after therapy, taste impairment and frequency of subjective complaints increased significantly in neutron and photon treated patients, but were statistically equivalent.Results of this study indicate that gustatory tissue response, as measured by taste detection and recognition and intensity responsiveness, and the frequency of subjective complaints related to taste are statistically equivalent in patients before, during, or up to 2 months after they were given either neutron or photon radiation for tumors of the head and neck. Continued study of these patients will be necessary to determine the relation between acute and late gustatory tissue response in neutron patients are compared to photon patients.     

The effect of pilocarpine and biperiden on salivary secretion during and after radiotherapy in head and neck cancer patients.

PURPOSE: The influence of parasympathicomimetic pilocarpine and anticholinergic biperiden on salivation in patients irradiated for malignant tumors of the head and neck region was assessed in a prospectively designed clinical study. METHODS AND MATERIALS: Sixty-nine patients, irradiated for head and neck cancer with salivary glands included in the irradiation fields, were randomly assigned into three groups (A, B, and C). Group A consisted of patients receiving pilocarpine, group B of those who were receiving biperiden during radiotherapy and pilocarpine for 6 weeks after its completion, while group C comprised patients not receiving any xerostomy prevention therapy during or after radiotherapy. The quantity of secreted unstimulated saliva was measured before the beginning of radiotherapy, after 30 Gy of irradiation, on completed irradiation, and 3, 6, and 12 months after completion of radiotherapy. RESULTS: Saliva secretion has been found to be the least affected by irradiation treatment in the group of patients receiving biperiden throughout the course of radiotherapy. Six months after completed irradiation, the differences in the quantity of secreted saliva between groups C and B as well as between groups A and B were statistically significant (P = 0.002 and 0.05 respectively). In patients receiving pilocarpine during radiotherapy, and those in the control group, further decrease in saliva secretion was observed. One year after completed therapy, the quantity of secreted saliva could only be measured in the patients receiving biperiden during radiotherapy: it amounted to 16% of the average quantity of saliva secreted before the beginning of irradiation. CONCLUSION: It seems that the inhibition of saliva production during irradiation treatment and the stimulation after completed radiotherapy may contribute to the preservation of salivary gland function after therapy.     

De Gustibus: time scale of loss and recovery of tastes caused by radiotherapy.

PURPOSE: To quantify the prevalence and distress of taste loss at different intervals after radiotherapy (RT) for head and neck cancer. MATERIALS AND METHODS: In four different groups of head and neck cancer patients (73 patients in total), taste loss and distress due to taste loss were evaluated by taste acuity tests and taste questionnaires. Group 1 (n=17) was analyzed prior to RT. Groups 2 (n=17), 3 (n=17) and 4 (n=22) were at 2, 6 and 12-24 months after treatment, respectively. A cross-sectional analysis was performed between these four groups. RESULTS: Prior to initiation of RT (group 1), partial taste loss was observed in 35, 18 and 6% of patients for bitter, salt and sweet, respectively. At 2 months after RT (group 2), taste loss (partial or total) was seen in 88, 82, 76 and 53% for bitter, salt, sweet and sour, respectively. At 6 months (group 3), partial taste loss was seen in 71, 65, 41 and 41% (bitter, salt, sweet, sour) and after 1-2 years (group 4) in 41, 50, 27 and 27% (bitter, salt, sweet, sour). Distress caused by taste loss was most frequent in group 2 (82%). CONCLUSIONS: In this study, loss of taste after RT was found to be most pronounced after 2 months. Bitter and salt qualities were most impaired. Gradual recovery was seen during the first year after treatment. Partial taste loss still persisted 1-2 years after treatment and was responsible for slight to moderate discomfort.     

Prophylactic gastrostomy tubes for patients receiving radical radiotherapy for head and neck cancers: A retrospective review

Patients undergoing radical radiotherapy for head and neck cancers often experience significant complications. We sought to evaluate the impact of prophylactic gastrostomy tubes (PGTs) among these patients on four easily evaluable adverse outcomes, namely, absolute weight loss, percentage weight loss, admissions for nutritional reasons and treatment interruptions. A retrospective review was carried out on patients undergoing radical radiotherapy for primary head and neck cancers from September 1999 to October 2005 at the Wellington Blood and Cancer Centre (n = 71). PGTs were placed in 7 (10%) patients. Patients with PGTs were compared with the patients without PGTs (the control group) by univariate and multivariate analyses. By univariate analysis, there was no significant difference in absolute or percentage weight loss between those with PGTs and the control group. By multivariate analysis, those with PGTs lost 5.2% (P = 0.016) less weight than the control group. There were no significant differences between the two groups with regard to admissions for nutritional reasons or treatment interruptions. The use of PGTs can reduce weight loss in patients undergoing radical radiotherapy for head and neck cancers, and its use should be further evaluated in future studies.     

A prospective analysis of factors that influence weight loss in patients undergoing radiotherapy

Malnutrition occurs frequently in patients with cancer. Indeed, a variety of nutritional and tumor related factors must be taken into account in these patients. Recognizing this relationship, we aimed to prospectively evaluate the risk factors that influence weight loss in patients undergoing radiotherapy with oral nutritional supplementation and dietetic counseling. Weight loss of 74 patients during radiotherapy and 1 month after treatment was analyzed. Parameters such as age, gender, tumor location, tumor stage, Eastern Cooperative Oncology Group performance status （ECOG PS） score, and the use of chemotherapy were analyzed to evaluate their influence on weight loss. All patients underwent oral nutritional supplementation and dietetic counseling. Forty-six （65.7%） patients lost weight, with a mean weight loss of （4.73 ± 3.91） kg, during radiotherapy. At 1 month after treatment, 45 （66.2%） patients lost weight, presenting a mean weight loss of （4.96 ± 4.04） kg, corresponding to a （6.84 ± 5.24）% net reduction from their baseline weight. Head and neck cancer patients had a mean weight loss of （3.25 ± 5.30） kg, whereas the remaining patients had a mean weight loss of （0.64 ± 2.39） kg （P = 0.028） during radiotherapy. In the multivariate analysis, the head and neck tumor location （P = 0.005）, use of chemotherapy （P = 0.011）, and ECOG PS score of 2-3 （P = 0.026） were considered independent risk factors. Nutritional status and parameters, such as tumor location （especially the head and neck）, the use of chemotherapy, and the ECOG PS score, should be evaluated before radiotherapy because these factors can influence weight loss during radiotherapy and 1 month after treatment.     

Maintained Salivary Function after Brachytherapy in Patients with Head and Neck Carcinomas - Evaluation Using Quantitative Salivary Gland Scintigraphy

The purpose of this study was to determine whether or not salivary gland dysfunction occurs within the first three months after brachytherapy in patients with head and neck carcinoma. Of the 20 patients with head and neck squamous cell carcinoma included in this study, 11 were treated with brachytherapy and the remaining 9 patients received external irradiation. All the patients underwent a salivary gland scintigraphy before and after radiotherapy. The scintigraphic parameters of each major salivary gland were then compared before and after the radiotherapy. In the brachytherapy group, none of the scintigraphic functional parameters showed a significant change before and after the radiotherapy. In contrast, all of the parameters with the exception of the uptake ratio (UR) of the submandibular glands significantly decreased after external irradiation. This observation was to be expected owing to the different irradiation doses administered by the two techniques. The scintigraphic technique used to evaluate salivary gland function should be used in future intensity-modulated radiation therapy salivary-gland-sparing studies in order to evaluate both the acute and chronic effects of irradiation in head and neck cancer patients.     

Maintained salivary function after brachytherapy in patients with head and neck carcinomas--evaluation using quantitative salivary gland scintigraphy

The purpose of this study was to determine whether or not salivary gland dysfunction occurs within the first three months after brachytherapy in patients with head and neck carcinoma. Of the 20 patients with head and neck squamous cell carcinoma included in this study, 11 were treated with brachytherapy and the remaining 9 patients received external irradiation. All the patients underwent a salivary gland scintigraphy before and after radiotherapy. The scintigraphic parameters of each major salivary gland were then compared before and after the radiotherapy. In the brachytherapy group, none of the scintigraphic functional parameters showed a significant change before and after the radiotherapy. In contrast, all of the parameters with the exception of the uptake ratio (UR) of the submandibular glands significantly decreased after external irradiation. This observation was to be expected owing to the different irradiation doses administered by the two techniques. The scintigraphic technique used to evaluate salivary gland function should be used in future intensity-modulated radiation therapy salivary-gland-sparing studies in order to evaluate both the acute and chronic effects of irradiation in head and neck cancer patients.     

Late oral complications following radiotherapy for head and neck cancers

Radiotherapy is an important treatment modality for head and neck cancers, both as definitive treatment and as adjunct treatment after surgery. Complications are common after radiotherapy for head and neck cancer owing to irradiation of many normal tissues and structures with important functions related to daily activities. Of these, late oral complications are of particular concern because of their effect on many basic functions, such as speech and swallowing. Although late complications following radiotherapy have been recognized for many years, recent developments in the treatment of head and neck cancers may have a significant impact on the incidence and severity of late complications. This article examines the current issue of late oral complications after radiotherapy, with an emphasis on the impact of recent advances in cancer treatment.     

Late oral complications following radiotherapy for head and neck cancers

Radiotherapy is an important treatment modality for head and neck cancers, both as definitive treatment and as adjunct treatment after surgery. Complications are common after radiotherapy for head and neck cancer owing to irradiation of many normal tissues and structures with important functions related to daily activities. Of these, late oral complications are of particular concern because of their effect on many basic functions, such as speech and swallowing. Although late complications following radiotherapy have been recognized for many years, recent developments in the treatment of head and neck cancers may have a significant impact on the incidence and severity of late complications. This article examines the current issue of late oral complications after radiotherapy, with an emphasis on the impact of recent advances in cancer treatment.     

Erythropoietin for patients undergoing radiotherapy: a pilot study.

BACKGROUND AND PURPOSE: To evaluate the feasibility and efficacy of using recombinant human erythropoietin (rhEPO) to correct decreased hemoglobin levels in patients undergoing radiotherapy and to get an estimate of its influence on the efficacy of radiotherapy. MATERIALS AND METHODS: Fifty patients with cancer of the head and neck and the pelvis were randomized before radiotherapy to different rhEPO treatments (none, 3 x 150 U/kg per week i.v., 3 x 300 U/kg per week i.v. and 3 x 150 U/kg per week s.c.). Hematological parameters were evaluated weekly and the locoregional tumor control rates were determined in 38 patients with head and neck cancer. RESULTS: rhEPO-treated patients showed a significant increase in their hemoglobin values (0.7 g/100 ml per week). The rhEPO response was comparable for patients with cancer of the head and neck and the pelvis. A delayed recovery was seen when iron deficiency or impaired iron mobilization was present. No serious toxicity was observed. Locoregional tumor control was improved, although not statistically significantly, in those head and neck cancer patients who experienced a rapid rise of hemoglobin. CONCLUSIONS: Low hemoglobin levels can be safely and quickly corrected with rhEPO. This may improve the effectiveness of radiotherapy.     

Lhermitte's sign following head and neck radiotherapy

Lhermitte's sign is an uncommon sequel of radiotherapy to the cervical spinal cord. Although the exact mechanism underlying its occurrence remains unclear; it is felt to be the result of a temporary interference with the turnover and synthesis of myelin, leading to focal demyelination. We have undertaken a detailed analysis of the radiation delivered to four patients who developed the sign after irradiation for malignancies of the head and neck. Our data support the view that radiation dose is crucial to its development, but calculations using the linear-quadratic radiobiological model raise interesting questions regarding the dose-response relationship. In particular, we find that calculations of biologically effective doses are predictive of a late rather than an early normal tissue response. The onset of symptoms after irradiation was apparent in all four patients within 4 months, with resolution in all being complete within a further 6 months. The recognition of this benign transient form of radiation-induced paraesthesia and its differentiation from the later onset, progressive and unremitting symptoms associated with radiation myelopathy is essential in reassuring patients undergoing head and neck irradiation.     

Granulocyte macrophage–colony–stimulating factor mouthwashes heal oral ulcers during head and neck radiotherapy

Purpose: To evaluate the effectiveness of granulocyte macrophage–colony–stimulating factor GM-CSF mouthwashes in the epithelization of radiation-induced oral mucosal ulceration, control of pain, and weight loss.Methods and Materials: Twelve patients received curative radiotherapy for head and neck carcinoma. All had oropharyngeal and/or oral mucosa irradiation, with a median dose of 72 Gy (range 50–74), with conventional fractionation. A total of 300 μg of GM-CSF in 250 cc of water for 1 h of mouthwashing was prescribed. The procedure started once oral ulceration in the irradiation field was detected. Patients, examined twice a week, were evaluated for oral ulceration, pain, and weight loss. Blood tests were taken weekly during GM-CSF administration. A comparison was carried out with 12 retrospective case-matched controls.Results: In the GM-CSF group, mucosa ulcerations healed in 9 of 12 (75%) of the patients during the course of the radiotherapy. Fifty percent of the patients said they felt less pain during the GM-CSF treatment; 30% needed morphine. The mean and median weight loss as a percentage of baseline weight in addition to the actual weight were 4.2% and 3%, respectively (variation ranged between a gain of 1% and a loss of 13%). No GM-CSF–related side effects were found. In the case control group, in the 12 cases, oral ulcerations increased during radiotherapy and two patients needed intubation intake and hospital admission, as opposed to the GM-CSF group. The mean and median percentage of weight loss were 5.8% and 5%, respectively. Sixty percent of patients needed morphine, as opposed to 30% in the GM-CSF group.Conclusions: Granulocyte macrophage–colony–stimulating factor was effective in curing mucosal ulcerations during the course of radiotherapy. This is the first time we have seen a drug with this capacity. Although the GM-CSF seems to be effective in the control of pain, oral intake, and weight loss, we need further studies with a greater number of patients to confirm our premise. Double-blind trials are necessary for future research into the control of pain and weight loss.     

Quality of Life in Patients of Head and Neck Cancer During Covid 19

The Indian Institute of head and neck oncology, a charitable Cancer Centre under the Indore Cancer foundation, continued to offer treatment during the Covid pandemic. 44 head and neck cancer patients who underwent surgery with adjuvant radiotherapy and 43 head and neck cancer patients who underwent only radiotherapy as the primary line of treatment from March 2020 to May 2021, were selected for the purpose of this study. Patients who underwent treatment for head and neck cancer either by radiotherapy or by surgery followed by post-operative radiotherapy were analysed to evaluate quality of life. Feedback was obtained using a QOL questionnaire. The results were analysed against numerical scores. Pain, appearance, speech, swallowing, chewing taste sensation etc. were analysed. Fear and psychological discomfort remained the overriding aspect.     

Nutritional consequences of the radiotherapy of head and neck cancer

Nutrition-related complications of radiotherapy were evaluated in 74 head and neck cancer patients. Subjective changes of mouth dryness, taste, dysphagia, appetite, and food preferences were determined by questionnaire before and at weekly intervals during curative radiotherapy. Changes in body weight during therapy were also recorded. In addition, 24-hour dietary histories were taken from eight patients at the beginning and end of treatment. Results of the study indicate that patients were subjectively aware of nutritional problems prior to therapy and that therapy exacerbated these problems. As many as 25% of the patients experienced oral complications such as taste loss and/or dry mouth prior to initiation of radiotherapy. By the end of radiotherapy, over 80% of the patients were aware of oral and nutritional problems. Patients had an average weight loss of 5 kg prior to therapy; this loss of weight did not change during therapy. Diet histories of eight patients indicate significant caloric deficiencies early and late in radiotherapy. The oral and nutritional problems experienced by patients, even prior to therapy, support the idea that nutritional evaluation and maintenance are important not only during therapy, but prior to radiotherapy as well. Nutritional evaluation should be made a routine, integral part of therapy for every cancer patient.     

Radiation-related damage to dentition

Because of typical tissue reactions to ionising radiation, radiotherapy in the head and neck region usually results in complex oral complications affecting the salivary glands, oral mucosa, bone, masticatory musculature, and dentition. When the oral cavity and salivary glands are exposed to high doses of radiation, clinical consequences including hyposalivation, mucositis, taste loss, trismus, and osteoradionecrosis should be regarded as the most common side-effects. Mucositis and taste loss are reversible consequences, usually subsiding early post-irradiation, whereas hyposalivation is commonly irreversible. Additionally, the risk of rampant tooth decay with its sudden onset and osteonecrosis is a lifelong threat. Thus, early, active participation of the dental profession in the development of preventive and therapeutic strategies, and in the education and rehabilitation of patients is paramount in consideration of quality-of-life issues during and after radiotherapy. This Review focuses on the multifactorial causes of so-called radiation caries and presents possible treatment strategies to avoid loss of dentition.