Keywords cancer - glottis - dysphonia - laser - radiotherapy
Introduction
Laryngeal cancer is one of the most common head and neck cancers, with glottic carcinoma
representing the majority of cases.[1 ] Early detection and treatment of laryngeal cancer can lead to a cure rate ranging
from 80 to 90%.[2 ] With a survival rate of this magnitude, it is not unreasonable for patients and
ENT surgeons to focus not only on the disease, but also on the impact of the proposed
treatment on the speaking function of the preserved larynx, to provide realistic patient
expectations.[3 ]
Hence, clinical research over the past 25 years has focused on efforts to preserve
the laryngeal function, through improvements in single-modality approach of patients
with early glottic cancer.[2 ] Such treatment options include larynx-preserving surgery (transoral laser microsurgery
[TLM]) and irradiation (or their combination, when deemed necessary).
The aim of the present study was to assess the impact of single-modality treatment
(TLM or radiotherapy, respectively), or combination therapy for early glottic cancer
(EGC) on postinterventional voicing as well as to identify factors which might explain
the related perceptions. Sociodemographic parameters potentially associated with postinterventional
voicing in patients with EGC were also explored.
Patients & Methods
A prospective study was conducted at a tertiary university hospital, involving 108
patients who had been treated for EGC between 2012 and 2016. The patients had been
subjected either to TLM (n = 64) or external irradiation (n = 15) or had received both treatment modalities in combination (n = 29). The inclusion criteria involved: a) stage I or II of glottic cancer, b) age
≤ 78 years. This parameter ensured that patients would not be older than 80 years
old at the second follow-up appointment, thus minimizing age-related voice disorders,
c) absence of heart failure, chronic obstructive pulmonary disease, psychiatric, or
neurodegenerative disorders, and d) competency in reading, writing, and understanding
the Greek language.
The patients filled in the voice handicap index 10 (VHI-10),[4 ] which is a validated robust short version of the VHI used to quantify the patients'
perceptions of their voice disorders in relation to their actual severity,[5 ] both for screening and interpretation purposes. The questionnaires were completed
1 and 2 years after the respective intervention. The VHI-10 consists of 10 items,
which assess functional, physical, and emotional domains of voice disorders, in relation
to the postinterventional status of patients treated for EGC.[4 ] There are five possible responses to each item (never, almost never, sometimes,
nearly always, and always). Individual scores for each item range from 0 to 4, and
the total score from 0 to 40. Higher questionnaire scores reflect worse postinterventional
voicing and voicing-related quality of life. The questionnaire has been appropriately
validated for the Greek language (GVHI-10).[6 ] Completion time typically lasted around 15 minutes.
Preliminary statistic control of group data, both with the Kolmogorov-Smirnov and
the Shapiro-Wilk tests, was not suggestive of satisfying fitting to the normal distribution;
hence, non-parametric tests were used to perform the respective statistical analyses.
The Mann-Whitney test was used to compare the total VHI-10 scores, between the studied
groups, in the first and second post-intervention year. The Wilcoxon signed rank test
compared the total VHI-10 scores within the studied groups, between the 1st and 2nd postintervention years, and boxplots depicted the observed differences. The potential
association between sociodemographic parameters and postinterventional voicing was
assessed using the Kruskal-Wallis test for occupation, marital, and educational status,
the Mann-Whitney test for gender, and the Spearman correlation coefficient for age.
All analyses were performed using the SPSS Statistics for Windows, Version 25.0 (IBM
Corp., Armonk, NY, USA). Statistical significance was accepted at the level of 0.05.
The research protocol was submitted, and ethical approval was received by the ethics
committee of the university to which the Academic Hospital is affiliated, prior to
commencing data collection. The participants were asked to sign a consent form before
being enrolled in the study.
Results
Among the 108 patients who participated in the study, 88 were male and 20 were female.
The mean age was 61.95 ( ± 9.27) years, ranging between 45 and 78 years of age (in
accordance with the inclusion criteria).
Transoral laser microsurgery was associated with postinterventional dysphonia (VHI
score 13.89 ± 3.93), which, however, attenuated between the 1st and 2nd postintervention years (VHI score 12.50 ± 4.06) (p = 0.000) ([Fig. 1 ]). Similar results were obtained in irradiated patients, in whom the occurrence of
postinterventional dysphonia (VHI score 13.73 ± 1.79) mitigated in the 2nd postintervention year (VHI score 10.80 ± 1.78) (p = 0.000) ([Fig. 2 ]). In addition, TLM and radiotherapy demonstrated comparable postinterventional voicing,
in the 1st (p = 0.940) and 2nd (p = 0.196) postintervention years.
Fig. 1 Boxplot depicting the attenuation of dysphonia between the first and second postinterventional
year in patients treated with transoral laser microsurgery.
Fig. 2 Boxplot depicting the attenuation of dysphonia between the first and second postinterventional
year in patients treated with external irradiation.
No association between sociodemographic parameters and the attenuation of postinterventional
dysphonia was identified for either treatment modality. The respective analyses included
age (pTLM = 0.785, pR = 0.109), gender (pTLM = 0.178, pR = 0.819), occupation (pTLM = 0.808, pR = 0.477), marital status (pTLM = 0.823, pR = 0.235), and education (pTLM = 0.322, pR = 0.497).
By contrast, when patients treated with TLM were compared with those treated with
additional radiotherapy, they demonstrated worse voice quality in the 1st (p = 0.010) and 2nd (p = 0.048) postintervention years. Furthermore, the comparison between patients treated
with radiotherapy and those treated with radiotherapy additional to TLM resulted in
worse voice quality in the 2nd , compared with the 1st postintervention year (p = 0.000). Such patients were demonstrating a detrimental effect on speech intelligibility
in noise (p = 0.000) in the 2nd , compared with the 1st post-intervention year (p = 0.000).
Discussion
Appropriate treatment planning for EGC involves an initial selection between TLM and
external irradiation. However, a key characteristic of both the disease and the proposed
treatment is the related impact on voice quality. Bearing in mind that the primary
goal of any treatment strategy for EGC is securing local disease control, a secondary
aim would be to provide the best possible quality of postinterventional voicing. Nevertheless,
patients treated for EGC need to have realistic expectations, accepting the fact that
postinterventional dysphonia will occur, despite the minuscule proposed intervention,
and regardless of the utilized treatment modality. That is because TLM results in
loss of vocal cord tissue, while radiotherapy leads to vocal fold fibrosis and muscle
fatigue.[7 ] However, the ensuing dysphonia is expected to attenuate between the 1st and 2nd postintervention years, following either treatment modality.
Single-modality therapy, as opposed to the combination of TLM and radiotherapy, is
favored for patients suffering from EGC, regardless of the utilized treatment modality,[2 ] in terms of retaining better postintervention voice quality, provided, of course,
that no medical reason dictates their combined use. This approach is confirmed by
the results of the present study, following a two-angled comparison strategy. Indeed,
when TLM patients (n = 64) were compared with their TLM and radiotherapy counterparts (n = 29), the latter group demonstrated worse voice quality in both the 1st (p = 0.010) and the 2nd (p = 0.048) postintervention years. Furthermore, when radiotherapy patients (n = 15) were compared with their TLM and radiotherapy counterparts (n = 29), the latter group demonstrated a deteriorating voice quality in the 2nd postintervention year, in comparison with the respective outcomes of the 1st year after treatment (p = 0.000).
While the improvement of postoperative VHI-10 scores in patients with EGC treated
with TLM is well established and seems, in fact, to be extending well into the 2nd postoperative year,[8 ] meta-analyses have indicated that the perceptive and acoustic vocal quality of their
radiotherapy-only counterparts may be even better.[1 ]
[9 ] However, by applying element analysis of the VHI-10, the present study identified
that when these radical single-treatment modalities are combined, the postinterventional
intelligibility of the patients' speech in noisy environments may pose as the primary
parameter of voice handicap in the 2nd postintervention year (p = 0.000).
By contrast, the progress of postinterventional dysphonia in early glottic cancer
patients treated with single-modality approach, does not seem to be associated with
sociodemographic parameters, including age, gender, occupation, marital, or educational
status. This finding is quite important, taking the rising rates of laryngeal cancer
in women into account,[10 ] along with the population aging in Western societies, as socio-demographic parameters
related to occupation and marital status have been associated with laryngeal cancer
incidence per se,[11 ] while advanced age has been considered an independent predictor of worse overall
(hazard ratio = 1.4), and cancer-specific (hazard ratio = 1.2) survival in head and
neck patients, even in the presence of an otherwise fairly equal access to care.[12 ] Furthermore, a higher socio-economic level might lead to more timely perception
of symptom importance, earlier access to health and dental services, and thus diagnosis
of head and neck cancer at an earlier stage.[13 ]
On the other hand, quality of life considerations arising either from the disease,
and/or from the proposed treatment, need to be analyzed during pre-interventional
counseling, as they may be linked to socio-demographic factors, and exert leverage
on different aspects of patients' lives (i.e., social life, psychological well-being,
financial implications). The attenuation of post-interventional dysphonia in early
glottic cancer should be viewed in this context, taking into account the importance
of identifying voice outcomes as a function of time on patients'quality of life. Indeed,
patients and physicians should realize the non-linear course of postinterventional
improvement in voice handicap,[8 ] and acknowledge the optimal time of voice function return, which does seem to be
extending up to two years posttreatment, according to the results of the present study.
Strengths of the present study include the use of a validated questionnaire, with
a completion time not exceeding 15 minutes, along with a robust statistical analysis.
Limitations of the present study include its single-center setting, along with a slight
underestimation of the mean age of patients treated for early glottic cancer. The
former limitation is counterbalanced by the fact that the study took place at a tertiary
academic hospital, which accepts referrals at a nationwide level. The latter limitation
was inextricably related to setting the upper age limit for patient selection to 78
years. However, this age-related parameter ensured that patients would not be older
than 80 years old at the second follow up appointment, thus minimizing the potential
impact of age-related voice disorders.
Conclusion
Single-modality therapy, as opposed to the combination of TLM and radiotherapy, is
favored for patients suffering from EGC, regardless of the utilized treatment modality,
in terms of retaining better postinterventional voice quality. Postinterventional
dysphonia occurs, regardless of sociodemographic parameters, in patients treated for
EGC and should be taken into account during preinterventional counseling, as it may
exert leverage on the quality of patients' lives. Patients and physicians should realize
the non-linear course of postintervention improvement in voice handicap and acknowledge
the optimal time of voice function return, which does seem to be extending up to 2
years posttreatment.
