|Year : 2017 | Volume
| Issue : 1 | Page : 316-324
Factors affecting the quality of voice in early glottic cancer treated with
Abds El-Hay R El-Assy1, Mohamed A.S. Baraka2, Hossam El-Dessouky3, Ayman E Abd El-Aziz1, Ibraheem A Abd El-Shafy1, Hanan A El-Shourbagy Eissa MSc 1
1 Department of Otorhinolaryngology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Phoniatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
3 Department of Phoniatrics, Faculty of Medicine, Cairo University, Cairo, Egypt
|Date of Submission||19-Sep-2016|
|Date of Acceptance||13-Nov-2016|
|Date of Web Publication||25-Jul-2017|
Hanan A El-Shourbagy Eissa
Department of Otorhinolaryngology, Faculty of Medicine, Menoufia University, Menoufia, 32511
Source of Support: None, Conflict of Interest: None
The aim of this work was to prospectively and objectively analyze the factors affecting the quality of voice in early glottic cancer treated with radiotherapy (RT) in order to choose the best factors that can be considered to facilitate the best voice quality after RT.
Voice preservation is an important component in the management of early glottic cancer. RT has been the traditional treatment approach, and has resulted in both excellent control rates and voice preservation.
Patients and methods
Patients with cT1-T2-NoMo glottic cancer underwent voice quality assessment before treatment and after radical RT. Post-RT voice quality was compared with the voice at diagnosis and the voice of healthy individuals who served as controls. A comprehensive set of voice parameters were measured. The effects of age, smoking history, T stage, and anterior commissure involvement on pretreatment and post-treatment voice quality were analyzed.
The voice quality data of 50 patients were analyzed after treatment, and significant improvement was seen in the majority of measured parameters. However, perturbation parameters and harmonic-to-noise ratio remained inferior compared with those of controls. A history of smoking and anterior commissure involvement resulted in poorer voice parameters following RT. There was no significant impact of age alone. T2 tumors had an inferior voice quality before treatment, but it did not remain inferior after RT.
There is considerable improvement in voice quality after RT. Several factors may have specific effects on pretreatment and post-treatment voice quality.
Keywords: early glottic cancer, glottic cancer, radiotherapy, voice quality
|How to cite this article:|
El-Assy AHR, Baraka MA, El-Dessouky H, Abd El-Aziz AE, Abd El-Shafy IA, El-Shourbagy Eissa HA. Factors affecting the quality of voice in early glottic cancer treated with
radiotherapy. Menoufia Med J 2017;30:316-24
|How to cite this URL:|
El-Assy AHR, Baraka MA, El-Dessouky H, Abd El-Aziz AE, Abd El-Shafy IA, El-Shourbagy Eissa HA. Factors affecting the quality of voice in early glottic cancer treated with
radiotherapy. Menoufia Med J [serial online] 2017 [cited 2020 Feb 28];30:316-24. Available from: http://www.mmj.eg.net/text.asp?2017/30/1/316/211509
| Introduction|| |
Laryngeal cancer is the second most common form of cancer of the respiratory tract, with an estimated incidence of 5.1/100 000 cases in men worldwide in the year 2008 and a European incidence rate of 10/100 000. The age-standardized mortality (world standard) from laryngeal cancer in men is 2.2/100 000 .
Voice preservation is an important component in the management of early glottic cancer .
Radiotherapy (RT) has been the traditional treatment approach, and has resulted in both excellent control rates and voice preservation .
Newer conservative surgical approaches that allow preservation of voice (e.g., laser cordectomy) are now available for small unilateral lesions with equivalent control rates .
Relatively few studies have reported on the objective measures of voice quality in both treated and untreated patients with early glottic cancer. Few studies in post-RT patients have demonstrated that, despite improvement, voice quality often does not normalize .
The extent of improvement and the residual lacunae may be potentially affected by several factors. These include patient-related factors (age, smoking history), disease-related stage [anterior commissure (AC) involvement], and treatment-related factors (radiation dose and volume).
The aim of this work was to prospectively and objectively analyze the factors affecting the quality of voice in early glottic cancer treated with RT to choose the best factors that can be considered to facilitate the best voice quality after RT.
| Patients and Methods|| |
All patients gave written informed consent before inclusion in the study. Fifty subjects diagnosed to have early glottis cancer (cT1-T2-NoMo) and who were treated with RT in our hospital (outpatient clinic of the Phoniatric Unit, Menoufia University Hospital) were offered voice quality assessment as part of prospective evaluation.
Patients treated with radical RT alone and who underwent both pretreatment and post-treatment assessment (at 3 and 6 months after RT) were included in this study.
Fifty healthy volunteers matched for age and sex (but nonsmoking) without any known head and neck pathology served as controls.
The following subjects were excluded:
- Those who had undergone any surgical intervention (other than a diagnostic biopsy) for the vocal fold lesion
- Patients who had recurrent disease previously treated with surgery or RT or who had undergone no treatment evaluation.
All patients were treated with radical RT. The radiation field size was determined by the extent of disease.
For all T1 turners, small fields were used, including the primary disease with appropriate margins (small field radiotherapy).
For T2 tumors large fields were used depending on the disease extent (subglottic or supraglottic extension), including lymph node areas at high risk for metastasis (wide-field radiotherapy).
Beam-modifying devices were used according to the contour of the neck and the site of the lesion. Patients were treated on telecobalt or a 6 mV linear accelerator.
Delivered doses ranged from 55 to 70 Gy. The two most common fractionation schedules were 55 Gy in daily fractions of 344 cGy or 60–70 Gy using cGy daily fractions of 6250 cGy.
Voice quality assessments were done before RT at 3 and 6 months.
A subjective assessment was made using the modified GRBAS scale .
Auditory perceptual assessment (APA) was performed by two phoneticians and one otorhinolaryngologist using the 'modified GRBAS scale'. The following were assessed:
- Overall grade
- Register, habitual register: modal, falsetto, or fry; presence or absence of register break
- Character (quality): strained, leaky, breathy, irregular, an asthenia; pitch: overall increased or decreased or diplophonia
- Loudness: loud, soft, or fluctuating
- Glottal attack: normal, soft, or hard
- Associated laryngeal functions: cough, whisper and laugh.
Both loudness and pitch levels were scored on a seven-point scale as follows: severely reduced (1), moderately reduced (2), mildly reduced (3), normal (4), mildly elevated (5), moderately elevated (6), and severely elevated (7).
Breathiness, leakiness, irregularity, and overall grade were rated on a four-point scale as follows: normal (0), mild (1), moderate (2), and severe (3).
Diplophonia was evaluated on a four-point scale as follows: no (0), occasional (1), frequent (2), and constant (3).
Objective assessment was made using a laryngeal videostroboscope with a digitalized stroboscope system (Model KS-4200 Explorent; Kay Elemetrics Corporation, Lincoln Park, NJ), which consists of a Kay Elemetrics stroboscopic light source with both xenon and halogen (constant) light sources, and slow, fast, and locked modes for viewing the vocal folds in motion or in 'fixed' position within the vibratory cycle with a display of amplitude and fundamental frequency.
There are two foot pedal controls: the first one in red to start and end the recording and the second one in black to switch between the xenon (strobe) and halogen light sources.
A laryngeal microphone with an audio preamplifier for accurate pitch extraction over an extensive range was attached.
The laryngeal videostroboscope was also fitted with a rigid oral 90° telescope (Stuemer CE 0297, TOPCON CO., LTD., Japan), a soakable SN 2687 camera F21 CE, a fiberoptic light cable, and a color printer.
The software used was Scope View 5011 (Dr Speech for Windows, version 2.4U; Tiger DRS, Inc., Seattle, WA, USA).
All subjects underwent videostroboscopic examination of the larynx while seated. A 90° rigid endoscopic examination was performed, during which subjects were asked to sustain the vowel/i/in their chest register at a comfortable intensity, then similarly while phonating in their highest register.
Acoustic voice analysis
Acoustic analysis was performed in the computerized speech lab. It consists of an external module with high-speed dual-channel 16-bit A/D and D/A, the plug-in board with two high-speed digital signal processing integrated circuits, high-quality microphone (type shure 14 H), studio-quality speaker, and software to acquire, analyze, and play speech signals with excellent fidelity.
Computerized speech lab with acoustic analysis software (Multidimensional Voice Program) can import and analyze signal data with any sampling rate. The input and output digitals anti-aliasing and analog antialiasing support a wide range of sampling rates and frequencies.
While in the sitting position at a constant mouth-to-microphone distance of 20 cm, each subject was instructed to perform the following tasks.
For maximum phonation time (MPT), the patient was asked to take a deep breath and produce the midvowel/α/as long as he/she could.
For average fundamental frequency (F0), highest fundamental frequency (Fmax), lowest fundamental frequency (Fmin), jitter percentage (Jitt), shimmer percentage (Shim), amplitude perturbation quotient (APQ), and noise-to-harmonic ratio (NHR), the patient was asked to produce a comfortable sustained sound by saying 1, 2, 3 followed by a sustained/α/after he/she had cleared the throat.
For pitch perturbation quotient (PPQ), the patient was asked to glide from the lowest pitch to the highest one by producing the word whoop and to glide from the highest pitch to the lowest by producing the word boom.
The voice signal was considered adequate if it was free of overloads (red signals on the screen) and there was audible variation in pitch and loudness. Each task was repeated three times to obtain the mean and standard deviation for each parameter.
All data were collected, tabulated, and statistically analyzed using SPSS, 19.0, for Windows (SPSS Inc., Chicago, Illinois, USA) and MedCalc 13 for Windows (MedCalc Software BVBA, Ostend, Belgium).
Two types of statistics were determined: descriptive statistics (e.g., percentage, mean, and SD) and analytical statistics. Analysis was carried out with the following tests.
χ2-test: This was used to study the association between two qualitative variables.
Fisher's exact test: This is a statistical significance test used in the analysis of 2 × 2 contingency tables when at least 25% of cells have an expected number less than 5.
t-Test: This is a test of significance used for comparison between two groups with normally distributed quantitative variables.
Mann–Whitney U-test: This is a nonparametric test of significance used for comparing two groups with non-normally distributed quantitative variables.
Wilcoxon signed rank: This is a nonparametric test for testing two related samples of non-normally distributed data.
A P-value of 0.05 was considered statistically significant.
| Results|| |
While analyzing the effect of smoking on the parameters of APA in both the pre-RT and post-RT groups we found that there was an increase in the severity of dysphonia, breathiness, and roughness in smokers in the pre-RT group but to a lesser extent than that in the post-RT group, with high statistical significance, which revealed the effect of smoking on APA parameters in both groups. There was also a highly significant relation between smoking and pitch and loudness changes [Table 1].
|Table 1 Effect of smoking on auditory perceptual assessment of the studied cases before and after radiotherapy|
Click here to view
There was a high statistical significance between smokers and nonsmokers in both the pre-RT & post-RT groups in the parameters of AFF-Jitt-PPQ and NHR, whereas there was a lack of statistical significance when studying the effect of smoking on Shim and APQ in the pre-RT group, which showed high statistical significance in the post-RT group [Table 2].
|Table 2 Effect of smoking on acoustic analysis of the studied cases before and after radiotherapy|
Click here to view
As regards the effect of AC involvement on different parameters of APA we found that there was a highly significant relation between those with AC involvement and others who without involvement of AC when assessing the severity of APA parameters in both the pre-RT and post-RT groups. Leakiness and straining showed lack of relation between AC and non-AC involvement in the pre-RT and post-RT groups [Table 3].
|Table 3 Effect of anterior commissure involvement on auditory perceptual assessment of the studied cases before and after radiotherapy|
Click here to view
This table showed that there was high statistical significance between the group with AC involvement and that without AC involvement in both the pre-RT and post-RT groups in the parameters of AFF and PPQ, whereas there was a lack of significance when studying the effect of AC involvement on Shim, APQ, and NHR in the pre-RT group. The same parameters showed high statistical significance in the post-RT group [Table 4].
|Table 4 Effect of anterior commissure involvement on acoustic analysis of the studied cases before and after radiotherapy|
Click here to view
[Table 5] shows the effect of staging of glottic cancer on acoustic analysis of the studied groups. In the pre-RT group there was no significant difference between T1 and T2 glottic cancer as regards AFF, Shim, APQ, and NHR, whereas Jitt and PPQ showed better results in T1 than in T2 glottic cancer. In post-RT assessment there was a high significant relation between the staging of glottic cancer and all parameters of acoustic analysis.
|Table 5 Effect of stage of glottic cancer on acoustic analysis of the studied cases before and after radiotherapy|
Click here to view
| Discussion|| |
In our study we found that the quality of voice is significantly impaired in patients suffering from vocal fold cancer. The incomplete closure of vocal folds due to tumor results in the escape of unphonated air, making the voice breathy and harsh. It increases the component of noise, decreasing the oise-to-harmonic ratio (HNR). The pretreatment voice of the patients in the study group had a higher frequency and perturbation factors, and a lower intensity, MPT, and HNR. The proportion of patients with higher grades of breathiness, harshness, and dysphonia was higher when compared with the control population with RT-induced vocal fold edema, and this can be seen up to 6–8 weeks after treatment. These findings are in agreement with those of Brunelli et al. .
Policarpo et al.  and Lehman  found that in some cases edema may persist longer. Tumor resolution and RT can lead to scar formation and fibrosis in the long term. This may result in a poor vibratory source and diffuse stiffness in the vocal fold.
In this study when studied objectively three to six months after RT, significant improvement was observed in the intensity, frequency perturbation parameters, HNR, and MPT.
Intensity and MPT increased, whereas frequency and perturbation parameters decreased after treatment. This may be caused by a loss of tumor bulk enabling the vocal fold to vibrate more freely. This is in agreement with the findings of Potenza et al. , who mentioned that after a median observation time of 74.5 months 5-year and 10-year local control was 89% [95% confidence interval (CI)=70.7–93.1%] and 86% (95% CI = 68.7–89.6%), respectively. Larynx preservation rate was 91.8% (95% CI = 82.4–94.9%) at 10 years. Five-year and 10-year overall survival was 72% (95% CI = 50.4–79.2%) and 56% (95% CI = 48.7–64.3%), respectively. Maximum detected acute toxicity included G3 dermatitis (5.4%) and G4 dyspnea (1.8%). Late toxicity profile was mild. VHI-10 scores showed a mild voice disability in both groups, with no statistically significant difference (P = 0.12), even when investigating different domains. Patients treated with radiation had a lower deterioration rate in all parameters except low voice, interruptions of sound, and diplophony.
Breathiness also improved after RT. This finding is in agreement with that of Harrison et al. , who also observed decreased breathiness and increased strain in post-RT voice.
Several voice quality parameters remained impaired after RT when compared with healthy controls. These included certain intensity and frequency parameters, perturbation parameters (shimmer and jitter), as well as HNR. This may be because of post-RT edema or scarring at the tumor site.
Steoicheff  have reported similar findings after comparing post-RT patients with healthy volunteers.
Several factors may have an impact on the post-treatment voice quality, and the identification of these factors may help us better understand the dynamics of voice change in relation to radiotherapeutic management. We could not identify other studies in the literature that have specifically addressed the impact of patient disease and treatment-related factors on the different component of voice quality.
In this study, our aim was to analyze the effect of several of these factors on objectively assessed parameters of voice quality at both diagnosis and after RT.
Both perturbation parameters and the grade of dysphonia and harshness may be affected by the degree of edema and inflammation on the vocal folds. Continued smoking may have a negative impact on post-RT voice. Benninger et al.  noted an increased risk for poorer voice quality in patients who continued smoking during and after treatment.
There was no significant difference in voice quality parameters in older or younger patients after RT. This seems to suggest that disease-related or treatment-related parameters are more important than age-related changes in the context of early glottic cancer treated with radiation.
The voice quality in terms of perturbation parameters (jitter, shimmer) and HNR was better in T1 disease. This may be because of the bulk of the disease: T1 lesions are less bulky or are small in size, thus causing fewer changes in the air stream flowing through the glottis. T2 lesions may hamper the vocal fold approximation, causing more escape of unphonated air, resulting in greater disturbance of perturbation parameters.
The regression of disease following RT results in a greater improvement in individuals with T2 tumors, and the difference is no longer marked. Colton and Casper  mentioned that improvement in acoustic voice measures from the pretreatment period to the post-treatment period for patient with early glottic cancer may be attributed to removal of the cancer from the vocal folds.
When cancer is present on one or both vocal folds they typically vibrate irregularly and asymmetrically, not achieving full closure, causing excessive air to escape through the vocal folds. Consequently the voice signal has high amounts of jitter, shimmer, and spectral noise, making it sound rough. People with early glottic cancer may develop hyper functional vocal behaviors such as increasing laryngeal tension to compensate for their rough sounding voice. This is in agreement with Wolfe et al. 
In this study we investigated the effect of smoking on MPT, which revealed that there was highly statistically significant difference between smokers and nonsmokers in both the pre-RT and post-RT group. This is in agreement with Sataloff et al.  and Buist et al. , who mentioned that there is evidence to suggest that MPT decreases with physical changes associated with older age and smoking, as these factors can reduce vital lung capacity and, consequently, vocal power.
In their series Wiernik  and Teshima et al.  found that the prospect of local control of early glottic cancer depends mainly on T stage, the tumor size, and the presence/absence of AC involvement. However, the optimal treatment approach for such high-risk patients remains unclear.
Johansen et al.  and Zouhair  also found that AC involvement is known as a significant prognostic factor, and the reported 5-year local control rate in early glottic cancer patients with AC involvement ranges from 55 to 70%.
Shvero  showed that, anatomically, the AC is attached directly to the thyroid cartilage, which lacks a protective perichondrial lining as a potential tumor barrier. This barrier is a relatively weak area from the point of view of tumor dissemination, where the Broyles' ligament penetrates into the thyroid cartilage. On the other hand, Mendenhall  showed AC involvement that is not associated with decreased local control following RT. The reason for such discrepant reports are not clear.
In our study we found that there was high statistical significance between smokers and nonsmokers in both the pre-RT and post-RT group with respect to the parameters of AFF-Jitt-PPQ and NHR. This is in agreement with the findings of Sorensen and Horii  and Prout et al. , who mentioned that individuals who smoke more than 35 cigarettes a day present a seven-fold high risk for laryngeal cancer.
Feijo et al.  found a higher prevalence of histological changes (metaplasia, hyperplasia) in autopsied smokers than in nonsmokers. Also Feijo et al.  found in 148 autopsies that 83.3% of nonsmokers had a normal epithelium, whereas among heavy smokers the proportion was 30.6%.
| Conclusion|| |
There is an overall improvement in voice quality among early glottic cancer patients treated with RT. However, certain parameters may remain inferior to those in healthy controls. Pretreatment voice may depend on several patient-related and disease-related factors. A history of smoking and AC involvement resulted in poorer voice parameters following RT. There was no significant impact of age alone. T2 tumors had an inferior voice quality before treatment, but it did not remain inferior after RT. Long-term assessments will further elucidate the natural history of voice following RT for early glottic cancer.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Ferlay J, Bray F, Pisani P, Parkin D. GLOBOCAN 2000: cancer incidence, mortality and prevalence worldwide, Version 1.0
. Lyon: IARC Cancer Base No. 5, IARC; 2001.
Mendenhall WM, Werning JW, Hinerman RW, Amdur RJ, Villaret DB. Management ofT1-T2 glottic carcinomas. Cancer 2004; 100:1786–1792.
Spector JG, Sessions DG, Chao KS, Hanson JM, Simpson JR, Perez CA, Management of stage II (T2N0M0) glottic carcinoma by radiotherapy and conservation surgery. Head Neck 1999; 21:116–123.
Pradhan SA, Pai PS, Neeli SI, D'Cruz AK. Transoral laser surgery for early glottic cancers. Arch Otolaryngol Head Neck Surg 2003; 129:623–625.
Rovirosa A, Martinez-Celdrán E, Ortega A, et al
. Acoustic analysis after radiotherapy in T1 vocal cord carcinoma. A new approach to the analysis of voice quality. Int J Radiat Oncol Biol Phys 2000; 7:73–79.
Kotby MN. The accent method of voice therapy
. Vol. 3. San Diego, CA: Singular Publishing Group Inc. 1995; p. 55.
Brunelli A, Al-Refai M, Monteverde M, Borri A, Salati M, Fianchini A. Stair climbing test predicts cardiopulmonary complications after lung resection. Chest 2002; 121:1106–1110.
Policarpo M, Aluffi P, Brovelli F, Borello G, Pia F. Oncological and functional results of C02 laser cordectomy. Acta Otorhinolaryngol Ital 2004; 24:267–274.
Lehman JJ, Bles DM, B-nrnljenburg JH. An objective assessment of voice prodiiciion after radiation therapy for stage I squamous cell carcinoma of the glottis. Otolaryngol Head Neck Surg 1988; 98:121–129.
Potenza I, Franco P, Moretto F, Badellino S, Balcet V, Rossi G, et al.
Exclusive radiotherapy for early-stage glottic cancer: a single-institution retrospective analysis with a focus on voice quality. Anticancer Res 2015; 35:4155–4160.
Harrison LB, Solomon B, Miller S, Pass DE, Armstrong J, Sessions RB. Prospective computer-assisted voice analysis for patients with early stage glottic cancer: a preliminary report of the functional result of laryngeal irradiation. Int J Radiat Oncol Biol Phys 1990; 19:123–127.
Steoicheff ML. Voice following radiotherapy. Laryngoscope 1975; 85:608–618.
Benninger MS, Gillen J, Thieme P, Jacobson B, Dragovich J. Factors associated with recurrence and voice quality following radiation therapy for T1 and T2 glottic carcinomas. Laryngoscope. 1994; 104
Colton RH, Casper JK. Understanding voice problems. In: Colton RH, Casper JK, editors. A physiological perspective for diagnosis and treatment
[Vol. 254]. 4th
ed. Baltimore, MA: Lippincott, Williams and Wilkins; 2006:pp. 78–80.
Wolfe V, Fitch J, Cornell R. Acoustic prediction of severity in commonly occurring voice problems. J Speech Hear Res 1995; 38:273–279.
Sataloff RT, Spiegel JR, Hawshaw MJ. History and physical examination of patients' with voice disorders. In: Rubin JS, editor. Diagnosis and treatment of voice disorders
. New York, NY: Igaku-Shom; 1995. pp. 247–261.
Buist AS, Sexton GJ, Naggy JM, Robs BB. The effect of smoking cessation and modification on lung function. Am Rev Respir Dis 1976; 114:115–122.
Wiernik G. The predictive value of tumor classification compared with results of the British Institute of Radiology fractionation trial in the treatment of laryngopharyngeal carcinoma. Laryngoscope 1990; 100:863–872.
Teshima T, Chatani M, Inone T. Radiation therapy for early glottic cancer (T1NOMO): I. Results of conventional open field technique. Int J Radiat Oncol Biol Phys 1989; 17:1199–1202.
Johansen LV, Grau C, Overgaard J. Glottic carcinoma-patterns of failure and salvage treatment after curative radiotherapy in 861 consecutive patients. Radiother Oncol 2002; 63:257–267.
Zouhair A. Decreased local control following radiation therapy alone in early- stage glottis carcinoma with anterior commissure extension. Strahlenther onkol 2004; 180:
Shvero J. Tl glottic carcinoma involving the anterior commissure. Eur J Surg Oncol 1994; 20:557–560.
Mendenhall WM. T1-T2NO squamous cell carcinoma of the glottic larynx treated with radiation therapy. J Clin Oncol 2001; 19:4029–4036.
Sorensen D, Horii Y. Cigarette smoking, and voice fundamental frequency. J Commun Disord, 1982; 15:135–144.
Prout MN, Sidari JN, Witzburg RA, Grillonc GA. Head and neck cancer screening among 4611 tobacco users older than forty years. Otolaryngol Head Neck Surg 1997; 116:201–208.
Feijo A, Fernandes MC, Pereira JP, Behlau M. Histological study of human vocal fold in cadavers of finite adipose individuals. In: Behlau M, editor. The voice of the expert. Rio Janeiro: Revinter; 2001. p. 183-191.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]