The number of oral cavity and oropharyngeal cancer survivors is rising. By 2030, oropharyngeal cancers are projected to account for almost half of all head and neck cancers. Normal speech, swallowing, and respiration can be disrupted by adverse effects of tumor and cancer therapy. This review summarizes clinically distinct functional outcomes of patients with oral cavity and oropharyngeal cancers, methods of pretreatment functional assessments, strategies to reduce or prevent functional complications, and posttreatment rehabilitation considerations.
| IMRT | Intensity-modulated radiotherapy |
| TLM | Transoral laser microsurgery |
| TORS | Transoral robotic surgery |
| UADT | Upper aerodigestive tract |
Key points
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The number of long-term oral cavity and oropharyngeal cancer survivors is increasing. Speech and swallowing outcomes are critical survivorship end points.
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Pretreatment functional assessment is essential to plan rehabilitation and supportive care, to predict functional outcomes, and to select the modality of therapy most likely to maximize functional outcomes.
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Refinements in surgical reconstruction, conformal radiotherapy techniques, and preventive therapy can be used to reduce functional problems after treatment.
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Posttreatment rehabilitation requires individualized planning on the basis of standardized, instrumental assessments.
Introduction
The number of oral cavity and oropharyngeal cancer survivors is rising owing to the increased incidence of oropharyngeal cancer and improved survival rates. By 2030, oropharyngeal cancers are projected to account for almost half of all head and neck cancers. The oral cavity and oropharynx are essential to normal speech, swallowing, and respiration. This review summarizes the clinically distinct functional outcomes of patients with oral cavity and oropharyngeal cancers, methods of pretreatment functional assessments, strategies to reduce or prevent functional complications, and posttreatment rehabilitation considerations.
Introduction
The number of oral cavity and oropharyngeal cancer survivors is rising owing to the increased incidence of oropharyngeal cancer and improved survival rates. By 2030, oropharyngeal cancers are projected to account for almost half of all head and neck cancers. The oral cavity and oropharynx are essential to normal speech, swallowing, and respiration. This review summarizes the clinically distinct functional outcomes of patients with oral cavity and oropharyngeal cancers, methods of pretreatment functional assessments, strategies to reduce or prevent functional complications, and posttreatment rehabilitation considerations.
Overview of functional outcomes
Oral Cavity Cancer
Surgical resection remains the primary treatment for many cancers of the oral cavity. Surgery disrupts the complex anatomy and functions of the upper aerodigestive tract (UADT) and may lead to lifelong disability, despite advances in minimally invasive approaches and microsurgical reconstruction. Radiotherapy or chemoradiation, often delivered as an adjuvant therapy, exacerbates postsurgical effects by way of added fibrosis and neuromuscular insult.
Speech production is dependent on 4 processes: respiration, phonation, resonation, and articulation. Each process involves precise biomechanical coordination of multiple structures in the oral cavity and UADT. Consequently, the type and degree of speech impairment varies depending on the location and extent of tumor within the oral cavity. In general, speech production is most adversely affected when oral cavity resections involve the mobile tongue or extend to include the soft palate.
Oral cavity cancers involving the tongue most commonly impair articulation. A recent systematic review suggested that speech remains largely intelligible (92%–98% intelligible at the sentence level [blinded ratings of unfamiliar listeners]) for most surgically treated patients with advanced-stage oral cancer (tumor category ≥T2), including those with tumors involving the tongue. Deviant speech characteristics were common findings across published studies, despite intelligible speech ratings. That is, data suggest that speech is largely understandable but not normal after surgical resection of advanced stage oral cancers. In addition, the extent of tongue resection greatly affects the accuracy of articulation and intelligibility. Most patients will ultimately acquire good intelligibility after partial or hemiglossectomy procedures that preserve half or more of the native tongue, but outcomes are more variable after subtotal and total glossectomy.
Treatment of oral cavity cancers can also disrupt speech resonance. Resections of cancers involving the maxilla cause significant rhinolalia until the oronasal defect is adequately sealed. Acceptable speech quality is achieved in most patients after successful prosthetic obturation or surgical reconstruction of the oronasal defect, but surveys find that self-reported speech function is still significantly lower in patients with cancer with maxillary defects relative to normal controls. In addition, obturation is typically less successful when the defect extends to involve the soft palate because of the soft palate’s dynamic involvement in the process of velopharyngeal closure.
Speech and swallowing function are closely related because they rely on common UADT structures. Swallowing occurs in 4 phases: oral preparatory, oral, pharyngeal, and esophageal. Treatment of oral cavity cancers most commonly affects the first 3 phases of swallowing. Oropharyngeal swallowing function can be impaired by the direct effects of oral cavity resection on oral preparatory functions (ie, mastication, collecting a bolus in the mouth) and oral transit (ie, posterior propulsion from the mouth to the pharynx). Oral cavity resection can also indirectly affect pharyngeal bolus transit by way of premature spillage that accompanies the loss of oral control, decreased lingual driving pressure on a bolus through the pharynx, or disrupted stabilization of the hyolaryngeal complex required for airway closure and upper esophageal opening. In addition, adverse effects of adjuvant radiotherapy or chemoradiation on pharyngeal swallowing function are well established. Data from a systematic review suggest that swallowing efficiency is commonly impaired after surgical management of advanced-stage oral cavity cancers (ie, prolonged bolus transit times and incomplete bolus clearance), but chronic aspiration is a less common consequence of surgical management (12%–25% prevalence). Therefore, it is not surprising that patients surgically treated for oral cavity cancer perceive the greatest degree of trouble swallowing dry or hard foods when polled about specific dysphagia symptoms.
Oropharyngeal Cancer
Survival after oropharyngeal cancer has dramatically improved in the past 20 years owing to intensified organ preservation strategies and the rising proportion of human papillomavirus-attributable cancer. Options for organ preservation include nonsurgical therapy (ie, radiotherapy and chemoradiation) and minimally invasive surgery (ie, transoral robotic surgery [TORS] or transoral laser microsurgery [TLM]).
Organ preservation strategies seek to achieve locoregional control and optimize functional outcomes. The oropharyngeal region is the crossroads where nasal, oral, laryngeal, and pharyngeal cavities meet. Swallowing function relies heavily on the coordinated response of these structures to propel a bolus safely from the mouth through the pharynx. Thus, pharyngeal dysphagia is the principal functional toxicity of treatment for oropharyngeal cancer, and is recognized as a key end point measure in the contemporary management of this disease. As Weinstein and colleagues noted, “…if it is found that the oncologic outcomes are equivalent…then the most important factor for triaging patients to TORS or chemoradiation will be swallowing outcomes.”
Swallowing is a complex biomechanical process involving 5 cranial nerves and more than 25 muscles in the UADT. Swallowing impairments can occur as the result of surgery alone, radiotherapy alone, or chemoradiation. Data specific to patients with oropharyngeal primary tumors demonstrate a high burden of dysphagia. In a population-based Surveillance, Epidemiology, and End Results–Medicare analysis of more than 8000 patients with head and neck cancer, patients with cancers of the oropharynx had the second-highest prevalence of dysphagia. In a pooled analysis of 3 Radiation Therapy Oncology Group chemoradiation trials, 35% of 101 patients with oropharyngeal cancer with adequate baseline function experienced late grade 3 or 4 laryngeal or pharyngeal toxicity, often including dysphagia.
Even in the era of conformal radiotherapy (ie, intensity-modulated radiotherapy [IMRT]) for oropharyngeal cancer, as many as 85% of patients require feeding tubes during therapy, and investigators report 6% to 31% rates of aspiration 1 year or more after treatment and 4% to 8% rates of chronic feeding tube dependence. In a trial evaluating treatment for oropharyngeal cancer with chemoIMRT that was designed to protect dysphagia-organs-at-risk using swallowing-specific dose constraints, 31% of patients had higher occurrences of aspiration 1 year or more after treatment relative to baseline, and 22% developed pneumonia. Aspiration was significantly predictive of pneumonia in this trial ( P = .017, sensitivity = 80%, specificity = 60%), and silent aspiration was evident on modified barium swallow (MBS) studies in 63% of patients who developed pneumonia. In addition, pharyngeal residue on MBS studies was significantly associated with the development of pneumonia after chemoIMRT ( P <.01).
Particularly concerning is the risk of severe, late radiation-associated dysphagia (late-RAD) that presents up to decades after radiotherapy in long-term survivors of oropharyngeal cancer. Although the prevalence of severe late-RAD is likely rare data suggest that the level of impairment is profound, often accompanied by a constellation of neuromuscular pathologies, including lower cranial neuropathies. In addition, late-RAD is largely refractory to standard, nonsurgical dysphagia therapies and leads to recurrent pneumonias requiring lifelong gastrostomy or elective functional laryngectomy.
TORS is emerging as a minimally invasive surgical alternative to nonsurgical organ preservation for oropharyngeal cancer, proposed to offer several functional advantages relative to open surgery or definitive chemoradiation. TORS allows access for resection without pharyngotomy or mandibulotomy, maintaining the critical muscular framework of the laryngopharynx. Tracheostomy, typically required for airway management after open resection, is also not needed for most patients who undergo TORS (70%–100%). Furthermore, published series suggest that 9% to 27% of patients treated with frontline TORS avoid postoperative radiotherapy and 34% to 45% avoid chemoradiation. Crude end points of functional recovery after TORS suggest promising early outcomes relative to radiation-based organ preservation regimens. Rates of percutaneous endoscopic gastrostomy tube placement (18%–23%) and chronic dependence (0%–7%) after TORS are lower than those reported for patients receiving definitive chemoradiation. However, patient-reported swallowing outcomes after TORS, according to the MD Anderson Dysphagia Inventory, are fairly similar to those of chemoradiation cohorts, and findings of gold-standard instrumental swallowing assessments are rarely reported after TORS. In addition, functional outcomes have been studied almost exclusively in the first year after TORS. Thus, further comparisons of long-term outcomes and swallowing outcomes based on instrumental examinations are needed to better understand the functional differences in surgical and nonsurgical organ preservation strategies for oropharyngeal cancer.
Pretreatment functional assessment
Pretreatment functional assessment is a critical component of comprehensive care. Baseline functional status has been shown to predict posttreatment functional outcomes. Finding of baseline functional assessments also, contribute to clinical decisions about supportive care to optimize treatment tolerance, such as the need for feeding tube placement prior to treatment or dietary changes necessary to prevent aspiration. Pretreatment functional status is also important to consider when selecting the modality of cancer therapy most likely to maximize functional outcomes, particularly when various modalities offer a similar likelihood of cure. Pretreatment examination by a speech pathologist should include, at a minimum, an oral motor/cranial nerve examination , motor speech evaluation (articulation, resonance, voice quality, speech intelligibility), and a clinical swallow evaluation . An instrumental swallowing examination is indicated in many cases, particularly in patients who present with advanced-stage primary tumors who have an increased risk of baseline aspiration. For patients with cancers of the oral cavity and oropharynx, the radiographic MBS study is the instrumental examination of choice because it allows evaluation of both oral and pharyngeal phases of swallowing. Laryngeal videostroboscopy is also useful in assessing laryngopharyngeal function, particularly in patients with advanced-stage oropharyngeal cancer that extends to involve the larynx.
Instrumental examinations are considered the gold-standard methods of assessment because they objectively assess oropharyngeal swallowing physiology and bolus transit, and predict adverse health outcomes (eg, pneumonia and malnutrition). Functional outcomes can also be assessed by patient-reported outcome (PRO) measures. PRO measures provide complementary data to instrumental or clinician-rated examinations, mainly regarding the impact of functional impairments on daily activities and quality of life. However, there is often a lack of agreement about the severity of impairment between subjective PRO measures and clinician-rated examinations, and PRO measures do not fully reflect true swallowing competency. Thus, the consensus is that both metrics (instrumental, clinician-rated examinations and PROs) should be combined for comprehensive evaluation of functional outcomes.
Standardized functional assessments offer critical data, but functional assessments lack uniformity in clinical practice and research. Minimum standards for functional assessment have been suggested on the basis of a recent systematic review to include the following measures, longitudinally assessed at least 3 to 4 times during the treatment trajectory of patients with oral cavity or oropharyngeal cancer: (1) instrumental/objective swallowing assessment (eg, MBS study) with supplemental clinical data, (2) assessment of speech intelligibility, (3) supplemental speech assessment of specific impairments relevant to oral cavity and oropharyngeal cancer (eg, articulation, resonance), and (4) PRO measures related to speech and swallowing. Table 1 describes various methods of pretreatment functional assessment.
| Pretreatment Functional Assessment | Domains Assessed |
|---|---|
| Clinical examinations | |
| Cranial nerve/oral motor examination | Symmetry/range of motion oral musculature Oral opening |
| Motor speech examination | Articulation Resonance Voice quality Subjective intelligibility rating |
| Clinical swallowing evaluation | Oral preparatory functions: mastication, oral containment, bolus consolidation Oral phase functions: oral control, oral clearance Pharyngeal phase functions (inferred): airway protection, pharyngeal transit |
| Instrumental examinations | |
| Modified barium swallow | Oral, pharyngeal, and laryngeal physiology Airway protection: laryngeal penetration, aspiration Pharyngeal transit: residue |
| Fiberoptic endoscopic evaluation of swallowing | Laryngeal and pharyngeal physiology Airway protection: laryngeal penetration, aspiration Pharyngeal transit: residue No direct observation of oral phase |
| Laryngeal videostroboscopy | Vocal fold mobility Symmetry, amplitude, periodicity Mucosal wave Laryngeal pathology |
Preventing or reducing functional problems
The severity of functional impairment can be influenced by a number of clinical factors. Current literature indicates that the percentage of oral tongue resection, type of reconstruction, contour of the free flap, and primary tumor stage affect postsurgical speech and swallowing outcomes. Functional outcomes also vary depending on the schedule of radiation, radiotherapy dose distribution, and the use of concurrent chemotherapy. Finally, swallowing outcomes can be influenced by supportive care practices, including the timing and type of feeding tube placement and the provision of targeted preventive exercise in patients receiving radiotherapy or chemoradiation. Disease characteristics (ie, subsite and tumor volume) that influence functional outcomes are unchangeable; thus, this section is focused on factors that can potentially be modified to prevent or reduce functional problems after treatment. These include surgical reconstructive factors, radiotherapy techniques, and supportive care/preventive therapy.
Surgical and Reconstructive Factors
Microvascular reconstruction is typically considered to benefit functional outcomes. Some studies, however, report significantly worse swallowing outcomes in patients who have reconstruction after oral cavity and oropharyngeal resections, largely due to the confounding effects of greater tumor burden and greater surgical defects in patients who require reconstruction rather than primary closure. Reconstructive factors that drive functional outcomes include sensory repair and the contour and volume of the flap.
Intraoral sensation has been shown to be correlated with UADT function, including pharyngeal swallowing competency, and sensory reinnervation can be performed during microvascular reconstruction.
Published studies report conflicting results regarding the functional outcomes of sensory reinnervation in oral cavity reconstructions. For instance, objective swallowing ratings according to MBS studies did not differ between patients with reinnervated flaps and those with noninnervated flaps in a prospective functional analysis of 44 patients. In contrast, Yu found significantly higher diet levels in patients with reinnervated anterolateral thigh flaps compared with those with noninnervated flaps after near-total or total glossectomy. Nonetheless, investigators have advocated that a relatively simple reinnervation procedure improves intraoral sensation and should be attempted when possible.
In addition, the shape and volume of the reconstructed tongue has been shown to affect postoperative speech and swallowing outcomes. Reconstructed flaps that are protuberant or semiprotuberant and those with greater volume are associated with significantly better speech intelligibility and dietary outcomes. On the basis of these findings, investigators have suggested overcorrection of the defect to account for volume loss that occurs with atrophy and postoperative radiotherapy. Finally, the utility of laryngeal suspension in patients requiring total or subtotal glossectomy has been demonstrated both to help protect the airway from aspiration and prevent prolapse of the flap.
Radiotherapy Techniques
Radiotherapy techniques can vary greatly, particularly the conformal methods used to spare normal tissue. Normal tissue constraints using IMRT have historically limited the dose to the salivary glands to reduce xerostomia. Swallowing-specific dose-constraints using IMRT have only recently been explored after a number of studies (most commonly in oropharyngeal cancer) elucidated the core swallowing-related organs at risk. The anterior oral cavity, superior pharyngeal musculature, and inferior larynx/esophageal inlet have been identified as swallowing-specific organs at risk, for which dose-volume coverage is correlated with short-term and long-term swallowing outcomes after IMRT. Data suggest that integrating swallowing-specific organ dose constraints into IMRT plans may reduce gastrostomy dependence, improve oropharyngeal swallowing efficiency, minimize aspiration, and optimize swallowing-related quality of life.
Pharyngeal and oral cavity constraints can be integrated into IMRT plans, whereas laryngeal dose-sparing can be achieved by integrating laryngeal dose constraints into full-field IMRT plans or a larynx block can be accomplished using a split-field technique. A split-field laryngeal block technique matches IMRT fields at the level of the arytenoid cartilages with a conventional supraclavicular laryngeal block (3 × 3 cm) using anteroposterior bilateral low neck fields. In patients with oropharyngeal cancer, the split-field technique has been shown to achieve a lower laryngeal and esophageal inlet dose compared with full IMRT fields. Current evidence supports the potential for laryngeal shielding and dysphagia-specific dose constraints to reduce the risk of dysphagia after conformal radiotherapy.
Preventive Therapy
Preventive swallowing therapy encourages ongoing use of the swallowing musculature during radiotherapy under the “Use it or lose it” paradigm. In preventive swallowing therapy, speech pathologists train patients to perform targeted swallowing exercises before and during the course of radiotherapy (although not during actual radiotherapy treatment sessions), and prescribe compensatory swallowing techniques or dietary modifications to discourage even brief NPO (nothing per oral) periods. Three randomized clinical trials have shown a benefit of early initiation of swallowing exercises during chemoradiation. One trial reported a 36% absolute risk reduction for loss of functional swallowing ability among patients randomized to receive swallowing exercises during chemoradiation. Favorable outcomes reported with preventive swallowing exercises include superior swallowing-related quality of life scores ; better base of tongue retraction and epiglottic inversion ; larger postradiotherapy muscle mass and magnetic resonance imaging T2 signal intensity of the genioglossus, mylohyoid, and hyoglossus muscles ; more normal oral diet levels after chemoradiation ; and shorter duration of gastrostomy dependence.
In addition, maintenance of any oral intake during radiotherapy (ie, avoidance of NPO intervals) has been found to independently predict long-term swallowing-related quality of life outcomes according to the MD Anderson Dysphagia Inventory and significantly predicts diet levels up to 1 year after radiotherapy. Multidisciplinary management of acute radiation toxicities, including odynophagia, dysgeusia, weight loss, and dysphagia, is necessary to help patients safely maintain oral intake during therapy. The evidence in favor of proactive swallowing therapy in patients with head and neck cancer who are treated with radiotherapy is summarized in Table 2 .
