|Year : 2018 | Volume
| Issue : 3 | Page : 208-213
Predictors of postradiation swallowing dysfunction in head-and-neck cancer
Romi Kant Grover1, Preety Negi2, Uttam Braino George3, Ashish Varghese4, Jaineet Sachdeva2, Pamela Alice Kingsley2
1 Department of Radiotherapy and Oncology, Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, India
2 Department of Radiation Oncology, Christian Medical College and Hospital, Ludhiana, Punjab, India
3 Department of Radiodiagnosis, Christian Medical College and Hospital, Ludhiana, Punjab, India
4 Department of Otorhinolaryngology, Christian Medical College and Hospital, Ludhiana, Punjab, India
|Date of Web Publication||17-Jul-2018|
Pamela Alice Kingsley
Department of Radiation Oncology, Christian Medical College and Hospital, Ludhiana, Punjab
Source of Support: None, Conflict of Interest: None
Background: Organ preservation protocols using concurrent chemoradiation therapy is increasingly utilized as a primary treatment for locally advanced head-and-neck cancers. Swallowing dysfunction has been recognized as the most common treatment-related quality of life (QoL) issue affecting 50%–60% of patients. Objective: The aim of the present study was to identify the factors that affect swallowing function after head-and-neck irradiation. Materials and Methods: From 2013 to 2014, 34 patients with squamous cell carcinoma head-and-neck region were prospectively enrolled in this study. The influence of the radiation treatment on swallowing function was evaluated using modified barium swallow test at baseline, 3 months, and 6 months. Chi-squared analysis was used to analyze the factors affecting swallowing function. Results: At 3 months following treatment, 76.5% of patients had swallowing dysfunction which decreased to 61.8% at 6 months. The statistically significant association was found between swallowing dysfunction and primary site in oral cavity and oropharynx (P = 0.04) at 3 months following treatment. Conclusions: While there is an ample literature reporting on several QoL issues for head-and-neck cancer patients, the various factors affecting swallowing dysfunction after the completion of treatment have not been fully described. Understanding the trajectory of swallowing dysfunction is important in identifying patients at high risk of protracted swallowing dysfunction. Providing appropriate early anticipatory intervention may improve patient's QoL. Longer follow-up is required to confirm these predictors of swallowing dysfunction.
Keywords: Chemoradiotherapy, head-and-neck neoplasms, quality of life, squamous cell carcinoma, swallowing dysfunction
|How to cite this article:|
Grover RK, Negi P, George UB, Varghese A, Sachdeva J, Kingsley PA. Predictors of postradiation swallowing dysfunction in head-and-neck cancer. CHRISMED J Health Res 2018;5:208-13
|How to cite this URL:|
Grover RK, Negi P, George UB, Varghese A, Sachdeva J, Kingsley PA. Predictors of postradiation swallowing dysfunction in head-and-neck cancer. CHRISMED J Health Res [serial online] 2018 [cited 2022 Aug 8];5:208-13. Available from: https://www.cjhr.org/text.asp?2018/5/3/208/236903
| Introduction|| |
Head-and-neck cancers represent the 6th most common cancer worldwide with an estimated annual incidence of 6,33,000 cases and 3,55,000 deaths. Among the various treatment modalities available, organ preservation protocols using radiation therapy (RT) or concurrent chemoradiation therapy (CRT) has become the standard of care for locally advanced inoperable and/or unresectable oropharyngeal, hypopharyngeal, and laryngeal carcinomas. RT for head-and-neck carcinoma inevitably results in considerable dose being delivered to the critical structures necessary for normal swallowing, such as the tongue, soft palate, pharyngeal and laryngeal muscles, leading to mucositis, and dysphagia.,, Concurrent chemotherapy also enhances the treatment-related dysphagia, aspiration, or stenosis affecting the long-term survival of these patients.
On looking into the mechanism of swallowing process, it is well-known that this process occurs in oral, pharyngeal, and esophageal phases. The anatomy and physiology of oral cavity facilitates an oral preparatory phase of swallowing thereby pushing the bolus material toward the pharynx by the tongue. During pharyngeal and esophageal phases of swallowing, in which food and liquid are moved from the pharynx to the stomach through the esophagus. Posttreatment dysphagia has been recognized as the most common quality-of-life (QoL) issue affecting up to 50%–64% of patients. A major under-reported complication associated with a swallowing dysfunction is silent aspiration leading to severe pneumonia.,, Among the several available methods for assessing the swallowing function, the most common method employed is modified barium swallow test. The purpose of this study was to identify the various factors affecting the swallowing function following treatment with RT/CRT using a modified barium swallow test.
| Materials and Methods|| |
This study was conducted on 34 diagnosed patients with carcinoma of head-and-neck who presented to the outpatient radiation oncology clinic for radiation treatment at our institute from December 2013 to November 2014. Written informed consent was obtained before enrollment into the study after clearance by the ethics committee. These patients were required to meet the following inclusion criteria: histopathological diagnosis of squamous cell carcinoma of head and neck receiving RT/CRT as a part of cancer-directed therapy with a curative intent, Karnofsky Performance Status ≥70. Patients were excluded if they had: neurological disease affecting swallowing function, previous history of RT/CRT for malignancy of head-and-neck region, and patients with tracheostomy.
The pretreatment evaluation included a history, physical examination, complete blood counts, biochemical profile, direct laryngoscopy and biopsy, computed tomography/magnetic resonance imaging of face and neck, and baseline modified barium swallow test. Following dental prophylaxis, all patients were planned to receive external beam RT to a dose of 66–70 Gy in 33–35 fractions over 6.5–7 weeks. RT was delivered in a phased manner by 6MV linear accelerator either with conventional or three-dimensional conformal radiotherapy (3-DCRT) technique. Patients were simulated with a thermoplastic cast of head-and-neck region for immobilization. In conventional treatment planning, in Phase I, the primary and the draining lymph node regions were treated to a dose of 40 Gy/20 fractions/4 weeks was delivered 5 days in a week at 2 Gy/fraction. In Phase II, off-cord boost was done, and a dose of 20 Gy/10 fractions/2 weeks was delivered over 12 days at 2 Gy/fraction. In Phase III, an additional dose of 600 cGy – 1000 cGy/3–5 fractions/3–5 days was delivered to the original primary tumor site. Treatment planning for patients receiving 3-DCRT involved contrast-enhanced planning computed tomography scan of the area of interest with 3 mm slices. Delineation of various target volumes such as gross tumor volume, clinical target volume, planning target volume, and organs at risk volume was done as per RT oncology group guidelines. Concurrent chemotherapy was administered to all patients with cisplatin of 40 mg/m 2 once every week or 100 mg/m 2 every 3-weeks until the completion of radiotherapy.
All patients underwent videofluorographic swallowing study, also known as a modified barium swallow test. During the procedure, the patient was either in sitting or standing position and was viewed in frontal and lateral planes. The fluoroscopy tube was positioned to view the oral cavity anteriorly, soft palate superiorly, posterior pharyngeal wall posteriorly, and the 7th cervical vertebra inferiorly. Four consistencies of food and liquid admixed with barium, i.e., liquid barium (thick and thin), processed diet (bread), and soft diet (mashed potatoes) were introduced by the teaspoon to the patient. The patients were instructed to hold the material in his/her mouth until told to swallow. The fluoroscope was kept focused on the oral cavity and pharynx during and after each swallow. In the oral preparatory phase, pharyngeal and cervical esophageal phases of deglutition were assessed and viewed simultaneously. Observations during each swallow were recorded which included as follows: (1) abnormal tongue movements, (2) abnormal swallowing, (3) laryngeal penetration, (3) premature spillage, (4) silent aspiration, and (5) aspiration. Laryngeal penetration was defined as any portion of the bolus entering the laryngeal vestibule to the level of the vocal folds. Premature spillage was defined as the leakage of food or fluid from the mouth into the pharynx before a voluntary swallow. Aspiration was defined as the passage of materials below the true vocal cord.
All patients were followed up for a minimum period of 6 months. At the 3rd and 6th month posttreatment, all patients underwent a modified barium swallow test.
| Results|| |
Median age was 55 years; range 22–75 years. The clinical and treatment characteristics are summarized in [Table 1]. All patients completed the planned course of definitive RT or CRT and modified barium swallow test except one patient who was lost to follow-up 4 months posttreatment. All patients received a dose of 66–70 Gy in 33–35 fractions over 6–6.5 weeks with weekly cisplatin of 40 mg/m 2 intravenous (iv) (47%) or 3-weekly cisplatin of 100 mg/m 2 iv (8%).
At baseline, 32.4% of patients exhibited the swallowing dysfunction on modified barium swallow test. The most frequently noticed disorders were abnormal tongue movements, abnormal swallowing, laryngeal penetration, premature spillage, silent aspiration, and aspiration [Figure 1]. Radiological pictures of silent aspiration and premature spillage has been shown in [Figure 2] and [Figure 3]. Several factors such as age, site of primary tumor, stage of disease, RT technique, and treatment modality were assessed to explore any association with the onset of swallowing dysfunction. Our results showed that the patients with primary involving the oral cavity and hypopharynx had a greater swallowing dysfunction as compared to oropharynx and larynx primary at 3 months and 6 months post-RT. In univariate analysis, we found that primary tumor location (P = 0.047) and RT technique employed (P = 0.039) statistically significant affected the swallowing function after the completion of treatment [Table 2] and [Table 3]. On applying binary logistic regression, it was found that only treatment type was significant with respect to the swallowing dysfunction at 3 months [Table 4]. No factor was found significant with respect to the swallowing dysfunction at 6 months [Table 5]. All data were analyzed using Chi-squared test SPSS software version 20.0 (IBM SPSS, Chicago, Illinois, USA).
|Figure 1: Modified barium swallow test findings at baseline, 3 months, and 6 months|
Click here to view
|Table 2: Association of patient, tumor and treatment-related factors with swallowing dysfunction on modified barium swallow test at 3 months posttreatment|
Click here to view
|Table 3: Association of patient, tumor and treatment-related factors with swallowing dysfunction on modified barium swallow test at 6 months posttreatment|
Click here to view
|Table 4: Binary logistic regression analysis of swallowing dysfunction at 3 months|
Click here to view
|Table 5: Binary logistic regression analysis of swallowing dysfunction at 6 months|
Click here to view
| Discussion|| |
Concurrent CRT has been recognized worldwide as the standard of care for patients with unresectable squamous cell carcinoma head-and-neck including patients with stage III and IV disease, younger than 70 years of age, and patients with good performance status., There have been remarkable advances in concurrent CRT as an organ preserving approach allowing many patients to hope for cure. The main emphasis of using concurrent CRT is about preserving the organ along with its function. The majority (82%) of our patients received concurrent CRT as the standard treatment for head-and-neck carcinoma.
However, the outcome of this therapy is not without treatment-related side effects. Swallowing dysfunction with head-and-neck carcinoma has been recognized as an important outcome. We observed that 32.4% of our patients had a baseline swallowing dysfunction; abnormal swallowing being the most common pattern noticed. According to the report by Logemann et al., the prevalence of pretreatment dysphagia was 28.2% in patients with stage T2 or more oral cancer, 50.9% in pharyngeal cancer, and 28.6% in laryngeal cancer. Aspiration has been recognized as the most frequent swallowing dysfunction in hypopharynx or larynx patients before initiating the treatment. Patients with worst baseline swallowing function were observed to have a higher rate of swallowing impairment.
Pharyngeal constrictors, glottis, and supraglottic larynx are the main structures responsible for dysphagia and aspiration after intensive RT/CRT. The probability of swallowing dysfunction increases to 19% with every 10 Gy additional RT dose to the constrictor muscles. All the patients in our study received a dose of 66–70 Gy.
In the present study, patients with carcinoma oral cavity or hypopharyngeal lesions had worse swallowing function compared to patients with other sites (oropharynx or larynx). We could attribute this finding to increased RT-related damage to the mucosa and soft tissue within the radiation treatment volume in these patients. There are several underlying causes for the swallowing dysfunction following RT. Soft-tissue inflammation, edema, pain, mucous production, and xerostomia are considered responsible for acute dysphagia during RT, while soft-tissue fibrosis, scar tissue formation, and neurological impairment can also result in decreased swallowing function after RT. The study findings are in contrast with findings from the study conducted by Langius et al. which reported that at 3 months posttreatment, patients with oropharyngeal tumors had a statistically significant worse activity for semisolids than patients with laryngeal tumors (43% for mild limitation vs. 73% for no limitation) (P = 0.01). These differences reduced at 6 months (74% vs. 86%) with the only minimal risk of airway penetration.
Dosimetric sparing of dysphagia aspiration-related structures (DARS) is an absolute prerequisite for improving the long-term swallowing function., In contrast to this, Lee et al. reported that no significant difference in pattern of dysphagia between patients with DARS and non-DARS primaries. Moreover, recently it has been shown that no clear treatment volume or dose constraints could be determined from the current available literature. The best possible way is to keep the radiation dose to these structures as low as possible.
Swallowing dysfunction and aspiration are the most worrisome sequelae associated with concurrent CRT. The consequence of these complications is a silent aspiration that could be highly variable, ranging from no adverse effect to airway obstruction, or severe pneumonia. We observed silent aspiration in 23.5% of patients at 3 months that reduced to 11.8% of patients at 6 months posttreatment. This is in line with the evidence that silent aspiration improves with time.
Among the various methods available for the swallowing assessment, modified barium swallow test is often considered as the method of choice by the most clinicians because it permits the visualization of bolus flow in relation to the structural movement throughout the upper aerodigestive tract in real-time. Keeping this in mind, we chose this method for the assessment of swallowing dysfunction in irradiated head-and-neck carcinoma patients.
Predicting group of patients that are likely to develop the swallowing dysfunction is challenging. Age, gender, associated comorbidities, primary tumor site, and treatment modality are all thought to influence the incidence of swallowing dysfunction in head-and-neck carcinoma patients. We found a statistically significant association between the tumor site and treatment modality affecting the swallowing function. Contradictory to this, in a study on identifying the risk factors for aspiration following treatment specifically for carcinoma oropharynx, the authors concluded that patients with larger tumors had a significant risk of developing aspiration following treatment.
In this study, 76.5% of patients had a swallowing dysfunction at 3 months assessment that improved in the next 3 months to 61.8% of patients. Deterioration of swallowing dysfunction continues to occur for as long as several years after CRT/RT treatment as a result of progressive fibrosis involving irradiated tissues of the head-and-neck.,
Currently, modern dysphagia-optimized RT techniques in head-and-neck cancer allow us to achieve a subsequent decrease in the treatment-related complications while improving the locoregional control rates. Unfortunately, even with these modern RT techniques, posttreatment swallowing dysfunction is not an infrequent occurrence. We observed that with three-dimensional conformal technique, there was a statistically significant reduction in the incidence of swallowing dysfunction compared to the conventional RT technique (P = 0.042). Recently doubts have been raised regarding the efficacy of advanced RT techniques in sparing swallowing structures such as pharyngeal constrictor muscles being responsible for meaningful functional organ preservation. Petkar et al. reported that intensity-modulated RT techniques that spare pharyngeal constrictor muscles should not be introduced into routine practice in view of lack of randomized evidence.
In the head-and-neck cancer treatment, maintaining a balance between disease control and functional impact on swallowing function positively affects the QoL. Recognizing potential risk factors such as primary tumor site could minimize the risk of swallowing dysfunction. In the present scenario, it should be mandatory to treat these patients with conformal technique, with the aim of a complete cure and minimizing swallowing dysfunction.
There are some limitations of this study that need acknowledgment, including small sample size and short follow-up period.
| Conclusions|| |
With the availability of effective treatment options, the survivorship and long-term QoL issues have become an area of active research in the head-and-neck carcinoma patients. A thorough evaluation of postradiation swallowing dysfunction should be considered as an integral component for optimal management of these patients. We infer from this study that identifying patients at risk depending on the location of a primary tumor and RT technique employed is crucial since these have a significant impact on minimizing swallowing function. However, the future prospective multi-institutional clinical trial is warranted to validate these results.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM, et al.
Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917.
Nuyts S, Dirix P, Clement PM, Poorten VV, Delaere P, Schoenaers J, et al.
Impact of adding concomitant chemotherapy to hyperfractionated accelerated radiotherapy for advanced head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys 2009;73:1088-95.
Garden AS, Harris J, Trotti A, Jones CU, Carrascosa L, Cheng JD, et al
. Long-term results of concomitant chemotherapy to hyperfractionated accelerated radiotherapy for advanced head and neck carcinomas: A phase II trial of the radiation therapy oncology group (RTOG 99 – 14). Int J Radiat Oncol Biol Phys 2008;71:351-5.
Manikantan K, Khode S, Sayed SI, Roe J, Nutting CM, Rhys-Evans P, et al.
Dysphagia in head and neck cancer. Cancer Treat Rev 2009;35:724-32.
Jain P, Kumar P, Pai VR, Parikh PM. Neoadjuvant chemotherapy or chemoradiotherapy in head and neck cancer. Indian J Cancer 2008;45:83-9.
] [Full text]
Jones K, Pitceathly RD, Rose MR, McGowan S, Hill M, Badrising UA, et al.
Interventions for dysphagia in long-term, progressive muscle disease. Cochrane Database Syst Rev 2016;2:CD004303.
Francis DO, Weymuller EA Jr., Parvathaneni U, Merati AL, Yueh B. Dysphagia, stricture, and pneumonia in head and neck cancer patients: Does treatment modality matter? Ann Otol Rhinol Laryngol 2010;119:391-7.
Hunter KU, Lee OE, Lyden TH, Haxer MJ, Feng FY, Schipper M, et al.
Aspiration pneumonia after chemo-intensity-modulated radiation therapy of oropharyngeal carcinoma and its clinical and dysphagia-related predictors. Head Neck 2014;36:120-5.
Mortensen HR, Jensen K, Grau C. Aspiration pneumonia in patients treated with radiotherapy for head and neck cancer. Acta Oncol 2013;52:270-6.
Xu B, Boero IJ, Hwang L, Le QT, Moiseenko V, Sanghvi PR, et al.
Aspiration pneumonia after concurrent chemoradiotherapy for head and neck cancer. Cancer 2015;121:1303-11.
Agarwal J, Palwe V, Dutta D, Gupta T, Laskar SG, Budrukkar A, et al.
Objective assessment of swallowing function after definitive concurrent (chemo) radiotherapy in patients with head and neck cancer. Dysphagia 2011;26:399-406.
Platteaux N, Dirix P, Dejaeger E, Nuyts S. Dysphagia in head and neck cancer patients treated with chemoradiotherapy. Dysphagia 2010;25:139-52.
Murphy BA, Gilbert J. Dysphagia in head and neck cancer patients treated with radiation: Assessment, sequelae, and rehabilitation. Semin Radiat Oncol 2009;19:35-42.
Essa HH, Azzam M. Concurrent chemoradiation in locally advanced head and neck cancers: A comparative study of weekly paclitaxel versus cisplatin-based regimen. J Egypt Natl Canc Inst 2010;22:165-73.
Georges P, Rajagopalan K, Leon C, Singh P, Ahmad N, Nader K, et al.
Chemotherapy advances in locally advanced head and neck cancer. World J Clin Oncol 2014;5:966-72.
Logemann JA, Rademaker AW, Pauloski BR, Lazarus CL, Mittal BB, Brockstein B, et al.
Site of disease and treatment protocol as correlates of swallowing function in patients with head and neck cancer treated with chemoradiation. Head Neck 2006;28:64-73.
Shune SE, Karnell LH, Karnell MP, Van Daele DJ, Funk GF. Association between severity of dysphagia and survival in patients with head and neck cancer. Head Neck 2012;34:776-84.
Eisbruch A, Schwartz M, Rasch C, Vineberg K, Damen E, Van As CJ, et al.
Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: Which anatomic structures are affected and can they be spared by IMRT? Int J Radiat Oncol Biol Phys 2004;60:1425-39.
Levendag PC, Teguh DN, Voet P, van der Est H, Noever I, de Kruijf WJ, et al.
Dysphagia disorders in patients with cancer of the oropharynx are significantly affected by the radiation therapy dose to the superior and middle constrictor muscle: A dose-effect relationship. Radiother Oncol 2007;85:64-73.
Schindler A, Denaro N, Russi EG, Pizzorni N, Bossi P, Merlotti A, et al.
Dysphagia in head and neck cancer patients treated with radiotherapy and systemic therapies: Literature review and consensus. Crit Rev Oncol Hematol 2015;96:372-84.
Langius JA, Doornaert P, Spreeuwenberg MD, Langendijk JA, Leemans CR, van Bokhorst-de van der Schueren MA, et al.
Radiotherapy on the neck nodes predicts severe weight loss in patients with early stage laryngeal cancer. Radiother Oncol 2010;97:80-5.
Petkar I, Rooney K, Roe JW, Patterson JM, Bernstein D, Tyler JM, et al.
DARS: A phase III randomised multicentre study of dysphagia- optimised intensity- modulated radiotherapy (Do-IMRT) versus standard intensity- modulated radiotherapy (S-IMRT) in head and neck cancer. BMC Cancer 2016;16:770.
Batth SS, Caudell JJ, Chen AM. Practical considerations in reducing swallowing dysfunction following concurrent chemoradiotherapy with intensity-modulated radiotherapy for head and neck cancer. Head Neck 2014;36:291-8.
Lee SY, Kim BH, Park YH. Analysis of dysphagia patterns using a modified barium swallowing test following treatment of head and neck cancer. Yonsei Med J 2015;56:1221-6.
Wang X, Eisbruch A. IMRT for head and neck cancer: Reducing xerostomia and dysphagia. J Radiat Res 2016;57 Suppl 1:i69-75.
Salama JK, Seiwert TY, Vokes EE. Chemoradiotherapy for locally advanced head and neck cancer. J Clin Oncol 2007;26:4118-26.
Eisbruch A, Lyden T, Bradford CR, Dawson LA, Haxer MJ, Miller AE, et al.
Objective assessment of swallowing dysfunction and aspiration after radiation concurrent with chemotherapy for head-and-neck cancer. Int J Radiat Oncol Biol Phys 2002;53:23-8.
Martin-Harris B, Jones B. The videofluorographic swallowing study. Phys Med Rehabil Clin N
Am 2008;19:769-85, viii.
Nguyen NP, Frank C, Moltz CC, Vos P, Smith HJ, Nguyen PD, et al.
Analysis of factors influencing aspiration risk following chemoradiation for oropharyngeal cancer. Br J Radiol 2009;82:675-80.
Bleier BS, Levine MS, Mick R, Rubesin SE, Sack SZ, McKinney K, et al.
Dysphagia after chemoradiation: Analysis by modified barium swallow. Ann Otol Rhinol Laryngol 2007;116:837-41.
Chang YC, Chen SY, Lui LT, Wang TG, Wang TC, Hsiao TY, et al.
Dysphagia in patients with nasopharyngeal cancer after radiation therapy: A videofluoroscopic swallowing study. Dysphagia 2003;18:135-43.
Petkar I, Bhide S, Newbold K, Harrington K, Nutting C. Dysphagia-optimised intensity-modulated radiotherapy techniques in pharyngeal cancers: Is anyone going to swallow it? Clin Oncol (R Coll Radiol) 2017;29:e110-8.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]