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ORIGINAL ARTICLE
Year : 2017  |  Volume : 13  |  Issue : 1  |  Page : 113-117

Acoustic analysis of voice in nonlaryngeal head and neck cancer patients post chemoradiotherapy


1 Department of Radiotherapy, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
2 Department of Speech Pathology and Audiology, National Institute of Mental Health and Neurosciences, Karnataka, India
3 Department of Radiotherapy, Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India

Date of Web Publication16-May-2017

Correspondence Address:
B K Yamini
Department of Speech Pathology and Audiology, National Institute of Mental Health and Neurosciences, Hosur Road, Bengaluru - 560 029, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.199386

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 > Abstract 

Background: Concurrent chemoradiotherapy (CCRT) used for definitive management of locally advanced head and neck squamous cell carcinoma (HNSCC) allows organ preservation at the cost of preservation of function. Vocal cords, being within the field of irradiation, undergo acute and chronic changes which adversely impacts the patients' voice.
Aims: To assess the acute changes in the acoustic characteristics of voice post-CCRT in patients with nonlaryngeal HNSCC.
Materials and Methods: Thirty patients with HNSCC treated with CCRT, a total dose of 66–70 Gy/33–35 fractions at five fractions/week, with weekly cisplatin. Acoustic analysis (AA) and laryngoscopic examination performed at baseline, 6 weeks, and 3 months post-CCRT. Statistical analysis of the parameters using ANOVA and Student's t-test was performed.
Results: Of the thirty patients, 26 patients completed CCRT. At 6 weeks post-CCRT, among 14/26 patients, most (11/14 [78.57%]) developed Grade III toxicity. On AA, both increase and decrease in mean F0 from baseline was observed. An increase (P < 0.05) in each, i.e., jitter, shimmer, and noise to harmonics ratio (NHR) were recorded. At 3 months post-CCRT, among 8/14 available, most (6/8 [75%]) showed Grade II toxicity. The mean F0 reduced for both genders; jitter and shimmer, and NHR values maintained an increase (P > 0.05).
Conclusions: Periodic AA allows quantification of voice changes and mapping of vocal toxicity induced by CCRT.

Keywords: Acoustic analysis, chemoradiation, head and neck cancer


How to cite this article:
Radhakrishna N, Yamini B K, Kadam AS, Shivashankar N, Vishwanathan C, Javarappa R. Acoustic analysis of voice in nonlaryngeal head and neck cancer patients post chemoradiotherapy. J Can Res Ther 2017;13:113-7

How to cite this URL:
Radhakrishna N, Yamini B K, Kadam AS, Shivashankar N, Vishwanathan C, Javarappa R. Acoustic analysis of voice in nonlaryngeal head and neck cancer patients post chemoradiotherapy. J Can Res Ther [serial online] 2017 [cited 2019 Nov 17];13:113-7. Available from: http://www.cancerjournal.net/text.asp?2017/13/1/113/199386


 > Introduction Top


Concurrent chemoradiotherapy (CCRT), the current standard of care for the definitive management of locally advanced head and neck squamous cell carcinoma (HNSCC), is worthly called an organ preservation technique.[1],[2] However, the normal tissue toxicity compromises the functional outcome of this treatment. The larynx is one such organ, whose function is affected due to its integral location within the field of radiation. Wide field head and neck irradiation adversely affects the voice, even in the absence of malignant laryngeal pathology.

Acute laryngeal toxicity induced by radiotherapy manifests as hoarseness of voice, pain in the throat and whispered speech with marked edema of the vocal cords and arytenoids, along with fibrinous exudates.[3],[4],[5],[6] Apart from the dose received by the larynx, the xerostomia and its associated reduction in pharyngeal lubrication also contribute to the vocal dysfunction.[7] Thus, radiation-induced dysphonia in the form of hoarseness, breathiness, voice breaks, repeated cough during speech, and whispered speech, impairs the patient's ability to communicate effectively, in turn, affecting the posttreatment quality of life (QoL).[8] The objective method of analyzing the voice changes has been through acoustic analysis (AA) and electoglottography.[9],[10]

The current prospective study was undertaken to assess the effect of CCRT on voice characteristics through AA. It allows quantification of the CCRT-induced changes in the acoustic characteristics of voice, which enable comparison of the laryngeal outcome of various chemo-radiation fractionation schedules.

Objective

To assess the acute changes in the acoustic characteristics of voice post-CCRT in patients with nonlaryngeal HNSCC.


 > Materials and Methods Top


Thirty patients with histologically proven squamous cell carcinoma of the head and neck with informed consent were enrolled. After ethical clearance, the study was conducted at the Department of Radiotherapy of a Government Medical College. They included patients aged between 18 and 70 years of both genders, with a Karnofsky Performance Score >70, who were planned to receive radical intent of treatment with a conventional fractionation schedule. Patients with primary laryngeal invasion, laryngeal cancers, comorbidities (diabetes mellitus, neurological ailments, etc.), postoperative cases, professional users of voice, and patients with preexisting vocal pathology were excluded from the study. Staging workup including confirmation of noninvolvement of laryngeal apparatus was performed by indirect laryngoscopy (IDL), nasopharyngolaryngoscopy (NPL), and radiological imaging.

Treatment protocol

Radical treatment to a total dose of 66–70 Gy in 33–35 fractions at 2 Gy/fraction/day was delivered along with weekly cisplatin. Posterior electron boost added where indicated.

Acoustic analysis

AA was performed at baseline, 6 weeks posttreatment, and 3 months posttreatment. The voice signal was recorded digitally using Computerized Speech Labs model 4500 (Kay Labs) on the Multidimensional Voice Protocol advanced version through a microphone (~12 cm mouth – microphone distance) with a sampling frequency of 50,000 Hz and resolution of 16 bits per sample. The patient was seated comfortably in a quiet room. Sustained phonation of vowel “|:aǀ,”| voiced thrice, at comfortable pitch and loudness was recorded with a pause of 60 s after each trial. Good samples of verified signals were saved for further analysis. The parameters of voice analyzed were fundamental frequency (F0), jitter, shimmer, and noise to harmonics ratio (NHR).

AA evaluates the signature characteristics of voice, namely the fundamental frequency (F0), jitter, shimmer, and NHR.[9] Laryngeal toxicities of CCRT in patients with nonlaryngeal HNSCC is evaluated by AA.[6],[7],[11] These studies have reported a significant worsening of acoustic parameters such as jitter, relative amplitude perturbation, amplitude perturbation quotient, pitch amplitude, spectral flatness ratio, and phonation frequency range. Similarly, aerodynamic measures such as mean phonation time, mean airflow, and vocal fold diadochokinetic rate were reported to have decreased among the nonlaryngeal group. Perceptual analysis of voice using the grade, roughness, breathiness, asthenia, and strain has also demonstrated a significant worsening of voice quality in the early postirradiation period in patients.[6],[11] Maximum phonation time and words per minute on AA and jitter on electroglottography have all shown a significant difference.[10] Such alterations in the voice have been found to have a profound impact on the voice-related QoL.[9],[11]

Statistical analysis

Pre- and post-treatment observations were analyzed using Student's t-test and ANOVA. Results on continuous measurements were studied by mean ± standard deviation. Significance was assessed at 5%.


 > Results Top


Flowchart of study patients is tabulated in [Figure 1]. The mean age of the cohort was 55 years. Twenty-three percent of the patients presented with T2 tumors, 40% with T3, and 37% with T4 tumors; primaries of the oral cavity and oropharynx being the most common.
Figure 1: Flowchart of the study patients

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Although all 30 patients had baseline AA, only 14 were available at 6 weeks post-CCRT and 8 patients at 3 months post-CCRT. Given this and to keep the homogeneity of patient numbers for comparisons, results were analyzed for different time periods separately, that is, for 14 patients from baseline to 6 weeks [Table 1] and for 8 patients from baseline to 3 months [Table 2].
Table 1: Acoustic analysis from baseline to 6 weeks

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Table 2: Acoustic analysis from baseline to 3months

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Baseline to 6 weeks post-CCRT: IDL examination of 14 patients revealed Grade II laryngeal toxicity in 3 patients and Grade III laryngeal toxicity in 11 patients [Figure 2]. AA demonstrated [Table 1] a decrease in the F0 from baseline in ten patients (five males and five females) and an increase in the F0 in four patients (two males and two females). There was a statistically significant increase in the jitter % (P = 0.03) and shimmer (in dB) (P = 0.009) and NHR (P = 0.02) in comparison with the baseline [Figure 3].
Figure 2: Comparison of laryngeal toxicity grades post CCRT

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Figure 3: Acoustic analysis from baseline to 6 weeks

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Baseline to 3 months post-CCRT: Ten patients were available out of which two patients underwent emergency tracheostomy because of Grade IV laryngeal toxicity. Endoscopic evaluation of eight patients revealed residual Grade I toxicity in two patients and Grade II toxicity in six patients [Figure 2]. AA showed a sustained increase in jitter, shimmer, and NHR compared to baseline (P > 0.05) [Figure 4]. The F0 values were lower than the mean baseline F0 for both genders, but not significant.
Figure 4: Acoustic analysis from baseline to 3 months

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 > Discussion Top


Our study aimed at understanding the effect of CCRT on the various acoustic parameters of voice. Kazi et al.[10] described the tumor-induced vocal cord edema and obstruction of airflow through the glottis that causes distortion of voice. Meleca et al.[12] have studied advanced laryngeal squamous cell carcinoma treated nonsurgically and described the tumor-induced neuromuscular weakness of the cords, which differs from the radiation induced mucositis and fibrosis of the laryngeal tissues. Thus, it was considered essential to rule out primary tumor affecting the laryngeal structures by performing IDL, NPL, and radiographic examinations at baseline.

At 6 weeks post-CCRT, IDL and NPL evaluation revealed marked edema of vocal cords, arytenoids, and false cords. Of the 14 patients available for analysis patients who had received a total dose of more >66 Gy had Grade III laryngeal toxicity. These findings support the study by Dornfeld et al.[13] who had shown a steep drop in the laryngeal function above a dose of 66 Gy delivered by intensity modulated radiotherapy (IMRT). Sanguineti et al.[14] recommend restricting the mean dose to larynx to <43.5 Gy at 2 Gy/fraction to minimize the risk of edema of Grade II and above. On univariate analysis, their study suggests the association of laryngeal edema with neck stage, nodal diameter, mean laryngeal dose, and laryngeal V30–V70 Gy. The patient reported voice outcomes used by Rinkel et al.[15] had also demonstrated deviant speech handicap index scores in 55% patients treated by IMRT/3-dimensional conformal radiation therapy. Current practices of larynx sparing techniques of IMRT by whole neck field IMRT or junctioned IMRT have allowed reduction of mean laryngeal doses between 29.1 and 38.8 Gy based on proximity to the larynx.[16] Laryngeal sparing was not feasible in patients with locally advanced primaries with nodal disease by conventional two-dimensional plans.

Evaluation of the vocal cords at the end of 3 months post-CCRT showed varying degrees of resolution of the vocal cord edema and erythema. Secretions were much lesser with the progression of time from treatment. These are attributed to the xerostomia, fibrosis, dehydration, and dryness of laryngeal mucosa.[4],[17]

AA has been used for objective assessment of voice by Hamdan et al.,[6] Paleri et al.,[11] and Fung et al.[7] While most studies have used the vowel |i| for analysis,[11] we have used sustained phonation of the vowel |a| for AA. AA performed at 6 weeks posttreatment revealed an insignificant decrease in the F0 in ten patients due to the increase in the effective mass of the cords due to edema in agreement with the findings of other studies [6],[7] which reported no significant change in F0. We also recorded an increase in the F0 in four patients (two males and two females) which may be attributable to the altered vibrational length of the cord due to the presence of mucositis-induced pseudomembrane. The jitter and shimmer values showed a significant increase from the baseline values. These reflect the alterations in the tissue of the vocal cords, which cause an increase in the perturbations of frequency and amplitude of its vibration. Thus, CCRT-induced edema alters the vibrational characteristics of the cords.

At 3 months post-CCRT, two out of the four patients who had shown an increase in the F0 values maintained the rise in comparison to the baseline. The remaining evaluated patients sustained a decrease in the F0 values as compared to the baseline. The jitter, shimmer, and NHR values showed an insignificant reduction in comparison to the values at 6 weeks although they did not return to baseline. However, Paleri et al.[11] reported a significant reduction in the F0 and a significant increase in both jitter and shimmer at 3 months post-CCRT; the same parameters evaluated at 1-year post-CCRT showed that the changes had reversed in direction although not to the baseline values. The present study reflects that the acute laryngeal toxicity induced by CCRT begin to settle around 3 months posttreatment. Long-term follow-up with a larger number of participants will be required to validate the same, as well as to identify the right time to initiate voice conservation in these patients.


 > Conclusions Top


Patients with nonlaryngeal HNSCC treated with CCRT experience significant alterations in the voice which can be objectively mapped using AA. However, larger sample size and long-term follow-up would be required to assess the long-term vocal toxicity, its impact on posttreatment voice-related QoL and measures necessary to reduce this toxicity.

Acknowledgments

We would like to acknowledge Dr. Iqbal Ahmed, Professor and Head, Department of Radiotherapy, Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

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Kulkarni MR. Head and neck cancer burden in India. Int J Head Neck Surg 2013;4:29-35.  Back to cited text no. 1
    
2.
Pignon JP, le Maître A, Maillard E, Bourhis J; MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients. Radiother Oncol 2009;92:4-14.  Back to cited text no. 2
    
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Sato K, Nakashima T. Effect of irradiation on the human laryngeal glands. Ann Otol Rhinol Laryngol 2008;117:734-9.  Back to cited text no. 3
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Berg EE, Kolachala V, Branski RC, Muller S, Johns MM. Pathologic effects of external-beam irradiation on human vocal folds. Ann Otol Rhinol Laryngol 2011;120:748-54.  Back to cited text no. 4
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Hamdan AL, Geara F, Rameh C, Husseini ST, Eid T, Fuleihan N. Vocal changes following radiotherapy to the head and neck for non-laryngeal tumors. Eur Arch Otorhinolaryngol 2009;266:1435-9.  Back to cited text no. 6
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Fung K, Yoo J, Leeper HA, Hawkins S, Heeneman H, Doyle PC, et al. Vocal function following radiation for non-laryngeal versus laryngeal tumors of the head and neck. Laryngoscope 2001;111 (11 Pt 1):1920-4.  Back to cited text no. 7
    
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Awan SN. The Voice Diagnostic Protocol: A Practical Guide to the Diagnosis of Voice Disorders. Maryland: Aspen Publication; 2001.  Back to cited text no. 9
    
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Kazi R, Venkitaraman R, Johnson C, Prasad V, Clarke P, Rhys-Evans P, et al. Electroglottographic comparison of voice outcomes in patients with advanced laryngopharyngeal cancer treated by chemoradiotherapy or total laryngectomy. Int J Radiat Oncol Biol Phys 2008;70:344-52.  Back to cited text no. 10
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Paleri V, Carding P, Chatterjee S, Kelly C, Wilson JA, Welch A, et al. Voice outcomes after concurrent chemoradiotherapy for advanced nonlaryngeal head and neck cancer: A prospective study. Head Neck 2012;34:1747-52.  Back to cited text no. 11
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Meleca RJ, Dworkin JP, Kewson DT, Stachler RJ, Hill SL. Functional outcomes following nonsurgical treatment for advanced-stage laryngeal carcinoma. Laryngoscope 2003;113:720-8.  Back to cited text no. 12
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Dornfeld K, Simmons JR, Karnell L, Karnell M, Funk G, Yao M, et al. Radiation doses to structures within and adjacent to the larynx are correlated with long-term diet- and speech-related quality of life. Int J Radiat Oncol Biol Phys 2007;68:750-7.  Back to cited text no. 13
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Sanguineti G, Adapala P, Endres EJ, Brack C, Fiorino C, Sormani MP, et al. Dosimetric predictors of laryngeal edema. Int J Radiat Oncol Biol Phys 2007;68:741-9.  Back to cited text no. 14
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Rinkel RN, Verdonck-de Leeuw IM, Doornaert P, Buter J, de Bree R, Langendijk JA, et al. Prevalence of swallowing and speech problems in daily life after chemoradiation for head and neck cancer based on cut-off scores of the patient-reported outcome measures SWAL-QOL and SHI. Eur Arch Otorhinolaryngol 2016;273:1849-55.  Back to cited text no. 15
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Webster GJ, Rowbottom CG, Ho KF, Slevin NJ, Mackay RI. Evaluation of larynx-sparing techniques with IMRT when treating the head and neck. Int J Radiat Oncol Biol Phys 2008;72:617-22.  Back to cited text no. 16
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