Research

Risk Factors For Voice Quality In Glottic Carcinoma (T1, T2) Following Curative Radiotherapy

¹ Roshan K Verma , ¹Nishikanta tripathi, ² Naresh K Panda, ³ Sushmita Ghosal, ⁴Anuradha Sharma

• ¹* Department of Otolaryngology, Head and Neck surgery;
• ²** Department of Radiotherapy;
• ³*** Division of Speech and audiology,
• ⁴Department of Otolaryngology,
• ⁴Post Graduate Institute of Medical Education and Research, Chandigarh, India- 160012.

• Saturday, November 23, 2013
• Friday, January 24, 2014
• Saturday, February 08, 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ((http://creativecommons.org/licenses/by/3.0)which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Abstract

Objective

To analyze various factors affecting the recovery of voice quality in patients of early glottic cancer (T1, T2 disease) before and after receiving curative radiotherapy.

Study Design

Prospective study carried out between Jan. 2010 – Dec. 2011.

Setting

The voice of patients of glottis carcinoma visiting our tertiary care hospital was assessed before and after radiotherapy and risk factors preventing return of voice to normal was assessed.

Methods

Fifteen patients of early glottis carcinoma (T1, T2) underwent voice assessment which included Perceptual analysis of voice by speech therapist and otolaryngologist, acoustic analysis of voice. Assessment was done prior to commencement of radiation therapy and at 1 month and 3 months following radiotherapy. Factors like smoking, anterior commissure involvement, stage of tumor and dose of radiation on the return of quality of voice was assessed.

Results

There was significant improvement in majority of the voice parameters post radiotherapy but the voice returned to normal in only 11% of the patients. Perceptual analysis (GRABAS) showed no difference in the quality of voice for smoking, stage of tumor, radiation dose and anterior commissure involvement. While acoustic analysis showed Smokers with glottic carcionoma had significant higher value of jitter before radiation than non-smokers and continued to remain higher even after radiotherapy. Jitter was seen to be significantly higher value in stage-II than stage I disease.

Conclusion

Voice quality improves following radiotherapy but not all the patients regain normal voice. Various factors affect the voice in patients of glottis carcinoma

Key words

Risk factor, voice quality, glottis carcinoma, radiotherapy

Introduction

Radiotherapy has historically been the gold standard for the management of early laryngeal cancer and results in high cure rates. The 5-year local control rates after radiotherapy vary from approximately 85% to 94% for T1 glottic carcinoma and from 70% to 80% for T2 lesions as reported by various authors1,2. The local control following radiotherapy depends on various factors including male gender [3], T stage of lesion [1], poor histologic differentiation [1], and prolonged treatment time [1].

There are multiple treatment options available for early glottic cancer which includes vocal cord stripping, cordectomy, other conservation laryngeal surgeries, endoscopic laser excision, and radiotherapy [4]. One of the major concerns during planning the management of early glottic carcinomas is voice of patient. Following radiotherapy voice of patient is preserved, although the quality of voice might alter [5]. In today’s scenario the importance of voice preservation goes beyond simply retaining the ability to vocalize. The quality of voice after treatment has assumed equal importance, as a determinant of both choice of treatment and quality of life following curative management. Radiotherapy does improve the voice in early glottic cancer, but does the voice returns to normal?

The quality of voice achieved after radiotherapy and factors that may have an impact on the quality of voice post radiotherapy has been poorly studied in literature. In this study, we have analyzed the impact of various factors that may eventually influence the quality of voice after radiotherapy.

Material and Method

This was a prospective study done to evaluate the factors that affect voice outcome following radiotherapy for early glottis carcinoma. An institutional review board’s approval was taken prior to undertaking this study. This study was conducted in the Department of Otolaryngology and Head and Neck Surgery, between Jan. 2010 – Dec. 2011. All patients suspected of early glottis carcinoma underwent detailed history and clinical examination; including fiber optic laryngoscopy and imaging. A detailed vocal assessment was done by speech pathologist and otolaryngologist. Pan-endoscopic assessment and biopsy under general anesthesia was done and single small punch biopsy of lesion was taken. Only histological confirmed cases of glottic carcinoma were sent for radiotherapy and rests were excluded from the study. A total of fifteen patients of early glottis carcinoma (T1 and T2) according to AJCC staging were included in the study. Various factors affecting voice quality in early glottic carcinoma i.e smoking history, stage of tumor, site of tumor and radiation dose was studied both pre and post radiotherapy.

Radiotherapy

After assessment of the voice, all the patients were referred for radiotherapy. All patients received curative dose of radiotherapy. The dose was 60-66 Grays, delivered over 30 to 35 fractions, over a period of 6 weeks. Small field radiation was used.

Vocal Assessment

Vocal assessment was done according to multidimensional voice protocol based on recommendation by European Laryngological Society[6]. which included:

1. Perceptual analysis of voice by speech therapist and otolaryngologist, by using GRBAS Scale [6]

2. Acoustic analysis using Dr Speech V3 Software for Windows 95. Acoustic parameters calculated were- F0 (Fundamental frequency), Intensity, Perturbation measures (jitter, Shimmer), HNR (Harmonic to Noise ratio), NNE (Normalised noise energy).

Follow Up

Baseline assessment of voice was done before radiotherapy and assessed for factors for factors affecting the voice quality.

Results

Total fifteen patients were included in study after thorough clinical, endoscopic, radiological assessment. All patients were classified as per TNM classification. Only male patients were included, as male and female voices are of different quality. 11 patients (73.3%) were smoker with pack years >10, 4 patients (26.7%) were non-smoker. (table 1).Distribution of the Site of tumor:

Table 1: Age distribution and smokers in glottis carcinoma

Age group (year)	40-50	51-60	61-70	total
Number of patient	6 (40%)	5 (33%)	4 (27%)	15 (100%)
smoker	5	3	3	11 (73.3%)
Non-smoker	1	2	1	4 (26.7%)

12/15 (80%) had involvement of single cord. Involvement of right and left were comparable.Both sides of cord were involved in 2/15(13.3%). Anterior commisure was involved in 5/15(33.3%)(table 2)

Table 2: Site of involvement

vocal cord status	Number of patients (%)
Only true cord involved	12 (80%)
True and false cord involved	3 (20%)
Right side involved	7 (46.6%)
Left side involved	6 (40%)
Both side involved	2 (13.3%)
Anterior commissure involved	5 (33.3%)
Impaired cord mobility	3 (20%)

Smoker and Nonsmokers

11 patients (73.3%) were smoker, 4 patients (26.7%) were non-smoker. The overall grade and severity of voice was similar in smokers and nonsmokers both before and after radiotherapy (p value>.05). We also found no statistical significant difference between smoker and non-smoker in other acoustic parameters except in the jitter value (table 5). There was statistical significant difference in pre radiotherapy jitter value between smoker and non smoker (p=0.02). Following radiotherapy jitter value though remained high in smokers, it was not statistically significant (p>0.05). (table 3)

Table 3: Voice quality in smokers Vs nonsmokers after radiotherapy

grade of voice	Smoker	Non smoker	Frequency mesures	smoker	Non- smoker	Perturbation measures	Smoker	Non-smoker
pre-RT	3	2	Habitual F0 Pre RT (HZ)	175.19	158.87	Jitter Pre RT (%)	1.05	0.19
1 mo. post RT	1	1	Habitual F0 3 mo post RT	142.2	166.4	jitter 3 mo post RT	0.43	0.38
3 mo post RT	1	1	SD-F0 Pre RT (HZ)	5.38	1.39	Shimmer pre RT (%)	5.7	3.7
Severity of voice			SD-F0 3 mo post RT	2.5	2.24	Shimmer 3 mo post RT	3.57	3.57
pre RT	5	5				SNR Pre RT	13.7	17.3
1 mo post RT	3	2				SNR 3 month post RT	15.08	16.92
3 mo post RT	2	2

Anterior commisure involvement

5 patients (33.3%) had anterior commissure involvement. The overall grade and severity of voice was similar in anterior commisure and without anterior commisure involvement both before and after radiotherapy (p value>.05).Acoustic parameter were also similar in both the both groups except SNR. SNR value differed significantly (p<0.05) following 3 months of radiotherapy between groups. Patient group without anterior commissure involvement showed higher SNR value.(table 4)

Table 4: Voice quality in anterior commimssure involvement

grade of voice	Ac involved	Ac free	Frequency measures	Ac involved	A c free	Pertubation measures	Ac involved	A c free
pre-RT	3	3	Habitual F0 Pre RT (HZ)	158.88	176.82	jitter Pre RT (%)	.51	.98
1 mo post RT	1	1	Habitual F0 3 mo post RT	149.2	148.4	jitter 3 mo post RT	.49	.38
3 mo post RT	1	1	SD-F0 Pre RT (HZ)	2.53	5.21	Shimmer pre RT (%)	4.4	5.5
Severity of voice	Ac involved	Ac free	SD-F0 3 mo post RT	2.4	2.4	Shimmer 3 mo post RT	4.4	3.1
pre RT	6	5				SNR Pre RT	15.7	14.2
1 month post RT	3	2				SNR 3 mo post RT	12.7	16.9
3 month post RT	2	2

Stage of tumor

9 patients (60%) had Stage I disease while 6 patients (40%) had stage II disease. Overall grade and severity of voice was similar in both groups both before and after radiotherapy. All other acoustic paramaters were similar in both groups except jitter. There was statistical significant difference in jitter at 3 months post RT between stage I disease and stage II disease. Acoustic parameters showed poorer values of jitter for stage II disease. SNR improved in both groups.(table 5)

Table 5: Voice Quality with Stage of Disease Before and After Radiotherapy

Grade of voice	Stage-I	Stage-II	Frequency measures	Stage-I	Stage-II	Pertubaton measures	Stage-I	Stage-II
Pre-RT	3	3	Habitual F0 Pre RT (HZ)	156.7	192	jitter Pre RT (%)	.67	1.0
1 mo post R T	2	2	Habitual F0 3 mo post RT	139.2	162.7	jitter 3 mo post RT	.34	.53
3 mo post RT	1	1	SD-F0 Pre RT (HZ)	3.58	5.4	Shimmer pre RT (%)	4.7	5.7
Severity of voice	Stage-I	Stage-II	SD-F0 3 mo post RT	2.0	2.9	Shimmer 3 mo post RT	3.6	3.4
Pre RT	5	5				SNR Pre RT	14.2	15.4
1 mo post RT	3	3				SNR 3 mo post RT	15.9	15.0
3 mo post RT	2	2

Radiation Dose

11 patients (73.3%) were treated with 60 Gy of total radiation and 4 patients (26.7%) treated with 66 Gy of total radiation dose. We found no statistical significant difference in the overall grade and severity of voice and frequency parameters. Acoustic parameters were also similar in both the group before and after radiotherapy. Radiation dose does not alter the quality of voice. (table 6)

Table 6: Voice quality with different doses of radiation

Grade of voice	Total dose (66 GY)	Total dose (60 GY)	Frequency measures	Total dose (60 Gy)	Total dose (66 Gy)	Perturbation Measures	Total dose (60 Gy)	Total dose (66 Gy)
Pre-RT	3	2	Habitual F0 Pre RT (HZ)	171.3	169.3	jitter Pre RT (%)	.80	.87
1 mo post RT	2	2	Habitual F0 3 mo post RT	138.1	177.4	Jitter 3 mo post RT	42	.41
3 mo post RT	1	1	SD-F0 Pre RT (HZ)	3.98	5.2	Shimmer pre RT (%)	5.2	4.8
Severity of voice	(66 Gy)	Total dose (60 Gy)	SD-F0 3 mo post RT	2.3	2.7	Shimmer 3 mo post RT	3.7	3.1
pre RT	6	5				SNR Pre RT	14.5	15.2
1 mo post RT	3	3				SNR 3 mo post RT	15.5	15.6
3 mo post RT	2	2

Discussion

The treatment of laryngeal cancer has evolved since past towards conservation laryngeal surgery, to organ preservation chemo-radiation protocol, to minimally invasive endoscopic treatment of the disease with an intention to improve quality of life by preserving speech, swallowing and an airway for breathing without tracheostoma [7]. Radiotherapy is the standard of care for early glottic carcinoma in present times while surgery is reserved for salvage in case of radiaton failure[8]. The aim behind this approach is to keep physiological functions like speech and swallowing intact to avoid morbidities.

Voice change in patient of early glottic carcinoma is a combined result of abnormal vibration pattern of vocal cords; incomplete glottic closure and impaired vocal cord mobility. These changes occur due to mass effect of tumour on vocal cords and infiltration of vocal cord by tumour. Curative radiotherapy improves voice in these patients by reducing the tumour bulk and subsequent improvement in vibration pattern but voice does not return to normal[9]. There are other factors in addition to the carcinoma larynx which may prevent the voice to return to normal after radiotherapy [10. An attempt was made to see the impact of these factors in our present study The effect of smoking on voice was compared in patients of carcinoma larynx. We found that overall grade of voice was much poorer in smoker with glottis carcinoma than nonsmokers with glottis carcinoma. Frequency measures also showed higher Habitual Fundamental frequency (habitual F0) as compared to nonsmokers. Pertubation measures also showed higher jitter and shimmer values in smokers with glottis carcinoma as compared to nonsmokers (table 1). After radiotherapy at 3 months, we found no difference in the grade, habitual frequency and shimmer between smokers and nonsmoker but jitter values remained higher in smokers after radiotherapy. Lehman et al [11]reported no significant association between smoking and voice quality following radiotherapy. Aggarwal et al10 reported that pre-treatment frequency parameters in smoker were significantly lower than non-smokers, and this pattern remained following radiotherapy. In contrary, frequency parameters were higher in smokers than nonsmokers in our study. Shimmer and jitter were worse in smokers than in non-smokers after radiotherapy, similar to our study [12,13].

The effect of anterior commissure involvement on voice was studied. We found no statistical significant difference in overall grade and severity of voice between patients with anterior commissure involvement and patients with anterior commissure free. Habitual and mean frequencies were found to be lower in anterior commissure involved group both before and after radiotherapy. Pertubation measures showed lower jitter and shimmer values in the anterior commisure involved group though statistically insignificant. However, patients with anterior commissure involvement had significantly lower value of SNR at 3 months post radiotherapy in comparison to those patients without anterior commissure involvement (p<0.05)

Stage of the glottis carcinoma also has effect on the voice post radiotherapy [14]. Patients with stage II disease had higher jitter and shimmer value than patients with stage I disease. Statistically significant difference in jitter was seen between stage I and stage II glottic carcinoma following 3 months post radiotherapy (p<0.05). Agarwal et al [10] reported that both shimmer and jitter were worse in stage II group prior to treatment, it persisted post radiotherapy though there was improvement in both groups similar to our study.

Radiation dose also has effect on the voice post radiotherapy [15]. However in our study, we found no statistical significant difference in overall grade of voice and severity of voice between patients who had received 60 Gy of radiation dose and patient group who had received 66 Gy of radiation dose for glottic carcinoma. Jitter, shimmer, NNE, HNR, SNR did not show significant difference between these groups post radiotherapy. In contrast Agarwal et al [10] in their study reported that patients who received higher dose radiation had higher jitter and shimmer values in comparison to that patient who received lower dose of radiation.

Conclusion

From our study we concluded

ØSmokers with glottis carcionoma had significant higher value of jitter before radiation than nonsmokers

ØAnterior commissure involvement:-significant lower value of SNR found

 ØStage of tumour:- jitter showed significantly higher value in stage-II disease following radiotherapy

ØRadiation dose:- statistically significant higher value of habitual frequency found at 3 months post radiotherapy in patients receiving 66 Gy of radiation than those who received 60Gy.

Authors' Contribution

RKV: conceptualized the study and drafted the manuscript and corresponding author

NT: conceptualized the study, collected data and did literature search

NKP: edited the manuscript

SG: Radiotherapist who planned and delivered the radiation dose, helped in preparation of manuscript.

AS: speech therapist and assessed the voice of all patients

Conflict of Interests

The authors declare that there are no conflicts of interests.

Ethical Considerations

Institute ethical committee approval was obtained for conducting this study. Informed consent was obtained from the individuals participating in the study.

Funding

None Declared

Acknowledgement

None

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