Introduction
Vocal fold (VF) immobility is a rare yet significant complication of radiotherapy (RT) for head and neck cancer. Aetiologies of immobility include radiation-induced neuropathy of the vagus or recurrent laryngeal nerve (RLN), soft tissue fibrosis and scarring, and cricoarytenoid (CA) joint (CA) ankylosis.Reference Huang and Chu1 The estimated latency period of cranial neuropathy following RT is variable, ranging from 1 to 34 years.Reference Jaruchinda, Jindavijak and Singhavarach2, Reference Crawley and Sulica3 Cricoarytenoid joint fixation is reported to have a similarly delayed onset.Reference Prepageran and Raman4 Presenting symptoms can range from chronic cough, hoarseness and vocal fatigue to severe airway obstruction, dysphagia and aspiration, each of which can significantly impact quality of life and patient safety. Given the clinical significance of VF palsy following head and neck RT, long-term follow-up is recommended.
Evidence on VF immobility following RT to the head, neck and mediastinum is primarily limited to case reports, case series and expert opinion.Reference Jaruchinda, Jindavijak and Singhavarach2–Reference Hsieh, Chang and Wang10 Most reported cases of RT-induced RLN paralysis occur in the setting of nasopharyngeal (NP) carcinoma.Reference Jaruchinda, Jindavijak and Singhavarach2, Reference Chaudhry and Akhtar7, Reference Lin, Jen and Lin11 Tumours of the oropharynx, larynx and thyroid, as well as lymphoma, are less commonly reported.Reference Crawley and Sulica3 The incidence of unilateral RLN paralysis after RT is estimated at 7.4 per cent, but the incidence of bilateral RLN paralysis is not well defined.Reference Jaruchinda, Jindavijak and Singhavarach2 While unilateral VF immobility is often managed effectively with medialisation procedures, bilateral vocal fold immobility (BVFI) presents a far greater clinical challenge. In these cases, patients must often choose between surgical airway optimisation at the expense of a functional voice or undergo a tracheostomy. Swallowing dysfunction is also commonly present. Optimal management strategies and the expected clinical course for such patients have not been well described in the literature.
We set out to analyse the clinical characteristics of patients with BVFI following head and neck RT at our institution. Our primary aim was to evaluate the clinical course of these patients, focusing on the timing of BVFI diagnosis after irradiation, airway management strategies and swallowing performance.
Materials and methods
All patients with a diagnosis of BVFI and a history of head and neck cancer treated with RT to the skull base and neck areas from January 2016 to July 2024 at NYU Langone Health were identified. Bilateral vocal fold immobility was defined as the complete immobility of both vocal folds. Only patients with bilateral, true VF immobility confirmed on flexible laryngoscopy were included. Patients with evidence of persistent or recurrent disease were excluded. Institutional Review Board approval was obtained from the NYU Langone Health Institutional Review Board. The data were de-identified, with no pertinent patient information.
Patients were identified through a retrospective search of the institutional electronic medical record using diagnostic codes and laryngology clinic records. All cases were assessed at the NYU Langone Voice Center by fellowship-trained laryngologists, with BVFI confirmed on flexible laryngoscopy. For the purposes of this study, the term BVFI is used to include both neurogenic and mechanical causes of reduced vocal fold movement, including CA joint fixation and post-radiation fibrosis, as formal palpation and laryngeal electromyography were not routinely performed.
Demographic data, primary tumour site, RT details (type, dosage in Gy and duration), chemotherapy regimen, documentation of bilateral VF mobility before or shortly after completion of RT, history of operative RLN sacrifice, presence of other cranial neuropathies and duration of follow-up were evaluated. The interval from RT completion to the onset of BVFI was documented. Airway interventions, such as tracheostomy, surgical airway procedures to avoid tracheostomy or to achieve decannulation, and time to decannulation post-RT were recorded. Results of instrumental swallow assessments (videofluoroscopic or fibre-optic endoscopic), history of aspiration pneumonia and primary means of nutrition were assessed. Recovery of VF mobility was determined by findings on flexible laryngoscopy at the last follow-up. Data were collected and analysed using Excel 2016 (Microsoft, Redmond, Washington, USA).
Results
Patient characteristics
During the study period, 12 patients were identified. The median age at the time of BVFI diagnosis was 65.8 years (range: aged 38–88 years), with a predominance of male patients (10, 83.3 per cent). The most common primary site of malignancy was the glottis (4, 33.3 per cent), followed by the nasopharynx (3, 25 per cent), thyroid (2, 16.7 per cent) and oropharynx (2, 16.7 per cent). Among the two patients with advanced thyroid malignancy, one had papillary thyroid carcinoma (PTC) and the other had anaplastic carcinoma. The majority of patients (11, 91.7 per cent) had documentation of bilateral, true vocal fold mobility, either prior to treatment or after treatment before development of BVFI. One patient with advanced PTC had a known unilateral, operative RLN sacrifice, had a unilateral immobility and then developed contra-lateral VF immobility after RT. All patients with glottic and hypopharyngeal carcinoma had normal mobility of the bilateral VFs before RT (Table 1). Two patients with NP carcinoma (15.4 per cent) had additional cranial neuropathies following RT (Table 2). These deficits included the abducens, facial, vagus and hypoglossal nerves. One of these patients had stage II disease; complete staging data for the other patient were unavailable.
Summary of 12 patients with BVFI following radiotherapy; BVFI = bilateral vocal fold immobility; VF = vocal fold; NPC = nasopharyngeal carcinoma; TC = thyroid carcinoma; BOT = base of tongue; SCC = squamous cell carcinoma; Chemo/RT = concurrent chemoradiotherapy; RT = radiotherapy; EBRT = external beam radiotherapy; IO = immunotherapy; RAI = radioactive iodine; Gy = Gray; Y = yes; N = no; x = unknown
Additional clinical factors and treatment detail of 12 patients with BVFI; BVFI = bilateral vocal fold immobility; RT = radiotherapy; IMRT = intensity-modulated radiotherapy; EBRT = external beam radiotherapy; RAI = radioactive iodine
Treatment detail and interval to diagnosis of bilateral vocal fold immobility
The majority of patients (11, 91.7 per cent) received intensity-modulated RT (IMRT), while one patient with advanced PTC (8.3 per cent) underwent external beam RT (EBRT) followed by radioactive iodine (RAI) therapy. The median radiation dose administered was 67.95 Gy (range: 27–70 Gy). One patient received 243 mCi of RAI. Two-thirds of patients (8, 66.7 per cent) received concurrent chemoradiotherapy. Regimens included combination carboplatin and paclitaxel (2/8), and cisplatin, with or without fluorouracil (2/8). One patient underwent immunotherapy after IMRT (Table 1). The median interval from RT completion to BVFI diagnosis was 7.5 years (range: 0.08–20 years), and the median follow-up duration was 6 years (range: 1–16 years) (Table 2).
Airway management
No patients recovered VF mobility. Approximately half (7, 58.3 per cent) required tracheostomy, and most tracheostomies were performed electively (5, 71.4 per cent), rather than emergently. The remaining patients without tracheostomy had a stable narrowed airway and did not require intervention. Among the two patients who were decannulated, one required cordotomy, arytenoidectomy and dilatations to maintain airway patency, while one refused intervention before decannulation (Table 3). The patient who refused intervention prior to decannulation ultimately underwent total laryngectomy due to a non-healing tracheocutaneous fistula and recurrent aspiration pneumonia. The 2 patients were decannulated 1.6 years and 13 years after completing RT.
Airway management
Swallow assessment and nutrition
Eight patients (61.5 per cent) underwent a videofluoroscopic study, and 4 (33.3%) underwent fibre-optic endoscopic examination. More than half of patients demonstrated oropharyngeal dysphagia (9, 75 per cent) or aspiration (8, 66.7 per cent). Eight patients experienced both. Of the 8 patients with aspiration, 7 (87.5 per cent) relied on percutaneous gastric tube (PGT) feeds for nutrition. All patients with evidence of aspiration on swallow assessment had a history of one or more episodes of aspiration pneumonia. One patient with aspiration declined enteral nutrition. One patient had oesophageal stenosis (1, 8.3 per cent) and required PGT placement. All PGTs remained in use for at least one year. Most patients who underwent tracheostomy also required PGT (5, 71.4 per cent). Three patients (25 per cent) had normal swallow (Table 4). Of these, two had T1–T2 glottic carcinoma, one of which had normal swallow both before intervention and after decannulation. The third patient had base of tongue carcinoma. The patient who underwent total laryngectomy was able to resume oral intake.
Swallow assessment and nutrition
Discussion
Bilateral vocal fold immobility is a rare complication of head and neck RT. The prevalence, timing of onset and optimal management have not been widely reported. Most large-scale studies on post-RT, lower cranial neuropathy discuss oropharyngeal and NP carcinoma, with the hypoglossal nerve most commonly reported.Reference Prepageran and Raman4–Reference Chaudhry and Akhtar7, Reference Lau, Lo, Wee, Tan and Low9, Reference Lin, Jen and Lin11–Reference Becker, Schroth, Zbären, Delavelle, Greiner and Vock13 In this institutional review, we present the largest cohort of patients diagnosed with post-RT BVFI and describe the clinical course of this complication. Our data show that RT-induced BVFI often has a delayed onset, limited recovery potential and a substantial impact on both respiration and swallowing.
The demographics of our study population are typical of other reports on RT-induced VF immobility, with a male predominance in the fifth and sixth decades of life.Reference Crawley and Sulica3 Glottic and NP carcinoma were among the most common sites of malignancy, aligning with prior reports.Reference Jaruchinda, Jindavijak and Singhavarach2 The median time from RT completion to BVFI diagnosis was 6 years, which falls within the reported latency range for post-radiation cranial neuropathies at other institutions (6.7–21 years).Reference Crawley and Sulica3, Reference Hutcheson, Yuk, Hubbard, Gunn, Fuller and Lai14–Reference Dong, Ridge, Ebersole, Li, Lango and Churilla16 Reported lag times for VF immobility due to CA joint fixation range from 11 to 15 years after RT.Reference Prepageran and Raman4, Reference Hsieh, Chang and Wang10 As laryngeal electromyography and palpation were not routinely performed, the precise aetiology could not be determined in this retrospective review. Nevertheless, BVFI is managed based on clinical manifestations, regardless of aetiology. The distinction between neurogenic and mechanical causes did not alter management in any case.
Prior studies have identified an inverse relationship between radiation dosage and the latency period of cranial neuropathy.Reference Stoll and Andrews17 Advanced T stage, radiation doses greater than 60 Gy, induction chemotherapy regimens and accelerated RT fractionation have been identified as predictors for late-onset neuropathy, following RT for oropharyngeal carcinoma.Reference Aggarwal, Goepfert, Garden, Garg, Zaveri and Du18 Our median cumulative dose of RT in patients who developed BVFI is in agreement with prior reports on radiation-induced neuropathy. Our study shows that despite the use of modern RT techniques and standard dosing protocols, the underlying pathogenesis of this late toxicity remains incompletely understood. Due to our sample size and study design, we cannot determine the prevalence of BVFI following IMRT by specific anatomical sub-site, though we suspect this distinction may be clinically relevant. Roughly three-quarters of patients in our sample underwent concurrent chemotherapy, which has been reported to increase toxicity of RT and tissue fibrosis, possibly contributing to RLN neuropathy, though data remain scarce.Reference Crawley and Sulica3, Reference Annino, MacArthur and Friedman19, Reference Kumar, Munjal and Panda20 Radioactive iodine therapy is generally believed to not impact VF mobility, though prior case reports comment on VF palsy following RAI for thyrotoxicosis with variable recovery.Reference Karabachev, Grohmann and Sajisevi21, Reference Beshyah, Al-Fallouji and Neave22 We are unable to comment on the contribution of RAI, chemotherapy and immunotherapy to BVFI due to the low number of cases in our cohort. As laryngoscopy is not typically performed in all post-RT patients with no prior laryngeal lesions or dysphonia, there may be sub-clinical VF motion abnormalities that remain undetected. Consequently, the true incidence remains unknown. Larger prospectively designed studies are needed to investigate the incidence and predictors of RLN neuropathy, following IMRT across pharyngeal and laryngeal sub-sites.
Vocal fold immobility significantly affects respiration, swallowing and quality of life. In this study, 53.8 per cent of patients with BVFI required tracheostomy due to stridor and dyspnoea. This figure is consistent with a prior case series investigating the clinical course of patients with BVFI across all aetiologies.Reference Brake and Anderson23 While one patient with tracheostomy opted to undergo endoscopic intervention to achieve decannulation, the majority did not. Management of BVFI post-tracheostomy includes multiple approaches such as cordotomy, arytenoidectomy or inter-arytenoid scar removal, depending on the aetiology. Up to 95.1 per cent of patients may be successfully decannulated following intervention.Reference Lechien, Hans and Mau24 A patient’s functional status and priorities, including maintenance of voice quality and swallow function, must be considered before any intervention aimed at decannulation.
Eight patients in our study required enteral nutrition secondary to aspiration or oesophageal stenosis. Our overall rate of swallowing impairment (66.7 per cent) exceeded that reported in one prior series examining BVFI across aetiologies (4 per cent), although only 3 of those patients had a history of RT.Reference Brake and Anderson23 The prevalence of symptomatic dysphagia among all post-RT head and neck patients and those with unilateral VF immobility is reported to be higher, ranging from 22 to 69 per cent.Reference Strojan, Hutcheson, Eisbruch, Beitler, Langendijk and Lee25, Reference Zhou, Jafri and Husain26 The high number of patients with oropharyngeal dysphagia, aspiration and PGT placement in our sample suggests that rates of symptomatic dysphagia in patients with BVFI may be higher than previously reported. The co-occurrence of tracheostomy and PGT placement (5/7, 71.4 per cent) aligns with the estimated prevalence in prior reports and highlights the further impact that tracheostomy may have on swallow function.Reference Skoretz, Anger, Wellman, Takai and Empey27 Swallow impairment in BVFI following irradiation is likely worsened by other RT-induced tissue changes, particularly pharyngeal and laryngeal fibrosis and sensory neuropathy.Reference Crawley and Sulica3 Prior studies using laryngeal electromyography to differentiate RLN from superior laryngeal nerve (SLN) injury reported that up to 67 per cent of post-RT BVFI patients may have concurrent SLN neuropathy.Reference Lau, Lo, Wee, Tan and Low9, Reference Hsieh, Chang and Wang10 While we did not directly evaluate SLN neuropathy, it is plausible that SLN injury and the bilateral nature of VF dysfunction contribute to a sub-set of our patients with aspiration. Vocal fold immobility preceding a diagnosis of dysphagia should be considered in irradiated patients.
Our study is subject to several limitations. This analysis is single institutional and retrospective. It is possible that patients required further intervention at other institutions that may not have been captured in our record, potentially leading to under-estimated data. The sample size is small, and data regarding pre-radiation VF mobility and RT detail were not available for all patients. Despite such limitations, our dataset allowed us to further elucidate the latency period and patterns of care among patients with BVFI following head and neck RT.
Conclusion
BVFI following head and neck RT often presents with a variable and prolonged latency period, significantly impacting airway patency and swallowing. In this study, a large proportion of patients required tracheostomy and enteral nutrition. These findings support prior literature and re-emphasise the importance of long-term follow-up for patients with a history of head and neck irradiation. Larger cohort studies are needed to better estimate the incidence and latency periods of BVFI by anatomical sub-site to improve patient care.
Financial support
This research received no specific grant from any fundraising agency, commercial or not-for-profit sectors.
Competing interest
The authors declared none.
Ethical statement and informed consent
This study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of NYU Grossman School of Medicine (#i24-00421). The requirement for informed consent was waived because of the retrospective design. The extracted data were de-identified with no pertinent patient information.
Author Contributions
All authors made substantial contributions in study design, collecting and analysing data, drafting and editing the manuscript, and reviewing all aspects of the work to ensure accuracy and integrity.
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