Pierre Delaere

The influence of xerostomia after radiotherapy on quality of life : Results of a questionnaire in head and neck cancer

IntroductionXerostomia is a common complication of radiotherapy for head and neck cancer because irreparable damage is caused to the salivary glands if they are included in the radiation fields. The aim of the study was to evaluate the degree of xerostomia in survivors of head and neck cancer and to determine its impact on quality of life.Methods and materialsA xerostomia questionnaire consisting of three parts (xerostomia score, quality of life survey, and visual analogue scale) was completed by 75 head and neck cancer patients, more than 6 months after radiotherapy and without evidence of disease.ResultsThe majority of patients (93%) suffered from a dry mouth, and 65% had moderate to severe xerostomia (grade 2 to 3). Both dysphagia (65%) and taste loss (63%) were common, although oral pain was less frequent (33%). The emotional impact of xerostomia was significant, causing worry (64%), tension (61%), or feelings of depression (44%). Furthermore, patients reported problems with talking to (60%) or eating with (54%) other people and to feel restricted in amount and type of food (65%). Quality of life was influenced by T classification, clinical stage, a higher radiation dose or the use of concomitant chemotherapy, but was independent of the interval since the end of radiotherapy.ConclusionsXerostomia after radiotherapy for head and neck cancer is extremely common and significantly affects quality of life. No recuperation is seen over time, and the use of concomitant chemotherapy significantly increases the oral complications of radiation. These results warrant the continuing efforts put into the development of salivary gland-sparing radiotherapy techniques and effective treatments of radiation-induced xerostomia.

HIF-1α, pimonidazole, and iododeoxyuridine to estimate hypoxia and perfusion in human head-and-neck tumors

PURPOSE: Tumor hypoxia measured by microelectrodes has been shown to indicate poor patient outcome. Here we investigated four potentially more widely applicable immunohistochemical parameters of tumor oxygenation and perfusion in human head-and-neck tumors. METHODS: Twenty patients with squamous cell carcinomas of the head and neck treated with primary surgery were injected with pimonidazole and IdUrd the evening before operation. Consecutive paraffin-embedded sections were stained for blood vessels, pimonidazole, IdUrd, and HIF-1alpha. IdUrd labeling and Ki-67 labeling around individual blood vessels were scored. The spatial relationship between HIF-1alpha and pimonidazole was studied, as well as the distribution of both markers as a function of distance from the nearest blood vessel. RESULTS: Measurement of all four parameters (diffusion-limited fraction, pimonidazole fraction, HIF-1alpha fraction, IdUrd-negative vessels) was feasible, and a significant difference between tumors was found for all parameters. IdUrd-labeled cells were absent around some vessels, indicating lack of perfusion, because these regions were positive for Ki-67. There was a positive correlation between diffusion-limited fraction and pimonidazole area for all images from all tumors, although no correlation for mean values per tumor. Colocalization of pimonidazole and HIF-1alpha was low (0.02%-25%). Most expression profiles showed a more homogenous distribution for HIF-1alpha than pimonidazole. There was no significant correlation between the pimonidazole and HIF-1alpha fractions in the 10 tumors studied. CONCLUSIONS: Simultaneous immunohistochemical measurements related to hypoxia and perfusion are feasible (and easily applicable) in resected human tumors. The different geographic distributions of HIF-1alpha and pimonidazole indicate that HIF-1alpha might not be suitable as a marker for chronic hypoxia. Each parameter will be correlated with outcome in a larger ongoing study on head-and-neck tumors treated with surgery with or without postoperative radiotherapy.

Acoustic analysis of the speaking voice after thyroidectomy

Voices of 47 female patients were analyzed before and after thyroidectomy, with preservation of the recurrent and superior laryngeal nerves and normal vocal fold motility during the observation period. A mean decrease of the speaking fundamental frequency (SFF) of 12 Hz was found on day 4; in 8 patients the postoperative vocal pitch was more than 2 semitones lower. The distance between the highest and lowest F0 during speaking was diminished (speech was more monotone) and the vocal jitter was elevated. In the frequency spectrum, there was a diminished prominence of the harmonics. The other spectral parameters (as the slope of the spectrum and the H1/H2 ratio) were unchanged. All changes had disappeared the fifteenth day, except for a lower SFF (> 2 semitones) in 2 cases. It is concluded that after normal dissection of the laryngeal nerves, and in the absence of vocal fold paresis, other reasons for voice changes immediately after thyroidectomy remain: alterations in the neck muscles, in the laryngeal mucosa, and in the patients general condition. Although the effects seem limited and of short duration, knowledge of them is helpful when informing the patient before thyroid surgery.

Tumoural perfusion as measured by dynamic computed tomography in head and neck carcinoma

PURPOSE To investigate the intra- and interobserver variability, as well as the intra- and interpatient variability of CT-determined tumour perfusion in head and neck tumours, and to evaluate the preliminary value of this parameter as predictive factor of local failure after treatment by definitive radiotherapy. MATERIALS AND METHODS In 41 patients the perfusion of a primary head and neck squamous cell carcinoma was estimated using dynamic CT. A 40-ml intravenous bolus of a low-osmolar non-ionic contrast agent was rapidly injected over 5 s (8 ml/s), while a dynamic acquisition of image data was obtained during the first pass at the level of the largest axial tumour surface. A time-density curve was constructed for the primary tumour and the carotid artery. The perfusion in the selected tumour region of interest was calculated by dividing the slope of the tumour-time density curve by the maximal value in arterial density. Tumour volume was calculated on the CT-images and correlated with perfusion rate. RESULTS The mean perfusion rate was 86.4 ml/min per 100 g (median, 80.6; SD, 43.05; range, 31.7-239.8 ml/min per 100 g). No systematic difference was found between the measurements performed by two independent observers. The intratumoural COV was 0.22, the intertumoural COV 0.37. No correlation was found with tumour volume. Ten out of 20 patients with a perfusion rate < 80 ml/min per 100 g were not locally controlled, while nine out of 21 patients with a value > 80 ml/min per 100 g did show a local failure (P = 0.19). CONCLUSIONS CT-determined perfusion measurements of head and neck tumours are feasible. No correlation with tumour volume and a sufficiently large COV were found to consider this parameter as a possible prognostic factor for outcome after radiotherapy. More patients need to be investigated to test the hypothesis that tumours with a low CT determined perfusion rate have a higher risk of local failure.

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.

Acoustic analysis of tracheo-oesophageal versus oesophageal speech

In order to evaluate the vocal quality of tracheo-oesophageal and oesophageal speech, several objective acoustic parameters were measured in the acoustic waveform (fundamental frequency, waveform perturbation) and in the frequency spectrum (harmonic prominence, spectral slope). Twelve patients using tracheo-oesophageal speech (with the Provox valve) and 12 patients using oesophageal speech for at least two months, participated. The main results were that tracheo-oesophageal voices more often showed a detectable fundamental frequency, and that this fundamental frequency was fairly stable; there was also a tendency to more clearly defined harmonics in tracheo-oesophageal speech. This suggests a more regular vibratory pattern in the pharyngo-oesophageal segment, due to the more efficient respiratory drive in tracheo-oesophageal speech. So, a better quality of the voice can be expected, in addition to the longer phonation time and higher maximal intensity.

Prognostic index for patients with parotid carcinoma: international external validation in a Belgian-German database.

Prognostic indices for recurrence‐free interval in patients with parotid carcinoma were developed and validated in a nationwide database. International validation would increase generalizability.

Experimental tracheal allograft revascularization and transplantation

The feasibility of tracheal allotransplantation with a fascial vascular carrier was examined in three groups with varied dose sequences of immunosuppression. A control group (group 1) received no medication. The three experimental groups were given daily cyclosporine intramuscular doses of 5 mg/kg (group 2), 5 mg/kg plus 3 mg/kg methylprednisolone (Solu-Medrol) (group 3), and 10 mg/kg (group 4) for 6 weeks or until death. Grafts were assessed by silicone dye infusion of the artery of the fascial flap to examine their microcirculation and by quantitative histologic study. Group 1 evidenced complete rejection after a heterotopic revascularization period of 14 days. The allografts of the experimental groups remained viable after 14 days of revascularization and could be transplanted orthotopically after this period. After transplantation, the viability of group 2 tracheas was unpredictable with changes ranging from mild to complete rejection. Group 3 evidenced well-preserved transplant viability with infection-induced necrosis at the anastomoses caused by the corticosteroid component. All group 4 animals survived the follow-up period with normal allograft viability. Cyclosporine in a dosage of 10 mg/kg per day can effectively suppress the immune response after transplantation of vascularized tracheal allografts. This experimental model will allow future studies to examine airway wall immunogenicity.

Impact of Adding Concomitant Chemotherapy to Hyperfractionated Accelerated Radiotherapy for Advanced Head-and-Neck Squamous Cell Carcinoma

PURPOSE To evaluate the feasibility and efficacy of a hyperfractionated accelerated radiotherapy (RT) schedule combined with concomitant chemotherapy (Cx) in patients with locally advanced head-and-neck squamous cell carcinoma. METHODS AND MATERIALS Between 2004 and 2007, a total of 90 patients with locoregionally advanced head-and-neck squamous cell carcinoma underwent irradiation according to a hybrid fractionation schedule consisting of 20 fractions of 2 Gy (once daily) followed by 20 fractions of 1.6 Gy (twice daily) to a total dose of 72 Gy. Concomitant Cx (cisplatinum 100 mg/m(2)) was administered at the start of Weeks 1 and 4. Treatment outcome and toxicity were retrospectively compared with a previous patient group (n = 73) treated with the same schedule, but without concomitant Cx, between 2001 and 2004. RESULTS The locoregional control (LRC) rate was 70% after 2 years. Two-year overall and 2-year disease-free survival rates were 74% and 60%, respectively. In comparison with the RT-only group, an improvement of 15% in both LRC (p = 0.03) and overall survival (p = 0.09) was observed. All patients were treated to full radiation dose according to protocol, although the Cx schedule had to be adjusted in 12 patients. No acute Grade 4 or 5 toxicity was seen, but incidences of Grade 3 acute mucositis (74.5% vs. 50.7%; p = 0.002) and dysphagia (82.2% vs. 47.9%; p < 0.001) were significantly higher in the chemoradiotherapy group compared with patients treated with RT alone. CONCLUSION With this chemoradiotherapy regimen, excellent LRC and survival rates were achieved, with acceptable acute toxicity.

Prospective randomized comparative study of tracheoesophageal voice prosthesis : Blom-Singer versus Provox

Objectives: Compare the most commonly used types of tracheoesophageal voice prostheses, Blom Singer and Provox. Study Design: Prospective study of 113 prostheses placed in 52 patients randomly selected to receive Blom‐Singer and Provox. Methods: Postoperative voice was recorded at 1 and 4 months after valve placement. Survival time of the prosthesis and four objective voice parameters were analyzed. Eight judges rated all recordings in a random order for six subjective voice parameters. Subgroup analysis for primary versus secondary placements and type of procedure was performed. In addition, patients were asked for their subjective assessment. Results: Overall, Blom‐Singer and Provox prostheses give very similar voice quality, lifetime, and patient satisfaction. Cleaning management is somewhat better for Provox, but there is a trend toward better overall voice quality for the Blom‐Singer prosthesis. In subgroup analysis secondarily placed prostheses score somewhat better than primary placements, and patients with total laryngectomy have better voices than patients with extended laryngectomy combined with partial pharyngectomy. Conclusions: Given the equal and good results in terms of voice quality, other factors (e.g., costs, surgery‐related factors, maintenance, patient preference) should be taken into account when deciding which type of tracheoesophageal voice prosthesis to use. Laryngoscope, 108:1561–1665, 1998